PATENT DOCUMENT

Abstract:
The invention relates to substituted diphenylamine compounds using as antitumor agents. The structure of the compounds is represented as the general formula (I): 
     
       
                 
         
             
             
         
       
     
     The groups are as defined as specification. 
     The compound represented by formula (I) showed potent antitumor activity, especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer.

Full Description:
FIELD OF THE INVENTION 
     The present invention relates to the field of medicine. Specifically to a substituted diphenylamine compounds and uses thereof as antitumor agents. 
     BACKGROUND OF THE INVENTION 
     The following compounds, which can be used as intermediates to synthetise a kind of multi-halogenated acridone compounds having fluorescence and pharmaceutical activity, were reported in patent CN101391981A. The invention discloses compounds KC1(IV-A), KC2(IV-B), KC3(IV-D), KC4(IV-E), KC5(IV-H) and KC6(IV-C), but there are no bioactivity reported. The compound KC1(XXIX) was also reported in  Pesticide Science  (1988), 24(2), 111-21, showing fungicidal activity against grape downy mildew ( Plasmopora viticola ). 
     
       
                 
         
             
             
         
      
     
     The compounds having the following general formulas were reported as insecticides, acaricides, fungicides, herbicides, rodenticide or others in the prior art: 
     
       
                 
         
             
             
         
      
     
     Such as patents BR7900462, CH626323, CN1188757, DE2509416, DE2642147, DE2642148, EP26743, EP60951, GB1544078, GB1525884, JP58113151, JP64001774, JP01186849, WO2002060878, WO2005035498, WO2009037707, U.S. Pat. No. 3,948,957, U.S. Pat. No. 3,948,990, U.S. Pat. No. 4,041,172, U.S. Pat. No. 4,152,460, U.S. Pat. No. 4,187,318, U.S. Pat. No. 4,215,145, U.S. Pat. No. 4,304,791, U.S. Pat. No. 4,316,988, U.S. Pat. No. 4,407,820, U.S. Pat. No. 4,459,304, U.S. Pat. No. 4,670,596 and so on, and ACS Symposium Series (1992), 504 (Synth. Chem. Agrochem. III), 336-48; Journal of the Chemical Society (1951), 110-15, etc. all reported the compounds having above general formulas. 
     In addition, the compounds of the following general formulas were mentioned in Chemische Berichte (1962), 95 1711-21; Chemische Berichte (1963), 96(7), 1936-44; Journal of Organic Chemistry (1954), 19, 1641-5; Journal of the Chemical Society; Transactions (1913), 103 982-8 and Journal of the Chemical Society, Transactions (1921), 119, 187-92 and so on, but without any bioactivity reported: 
     
       
                 
         
             
             
         
      
     
     The compounds having the following general formulas as fungicide were reported in patent WO2012171484: 
     
       
                 
         
             
             
         
      
     
     The compounds having the following general formulas as fungicide were reported in patent WO2011116671: 
     
       
                 
         
             
             
         
      
     
     The compounds having the structure of general formula I were not reported in the prior art as antitumor agents. 
     SUMMARY OF THE INVENTION 
     The object of the present invention is to provide substituted diphenylamine compounds having general formula I, which can be applied to antitumor agents. 
     Detailed description of the invention is as follows: 
     Substituted diphenylamine compounds use thereof as antitumor agents, the compounds having the structure of general formula I: 
     
       
                 
         
             
             
         
      
     
     Wherein: 
     R 1  is selected from H, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 halo alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8 alkylamino carbonyl, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 1 -C 8 alkylsulfonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxyC 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkylaminothio, C 2 -C 8 dialkylaminothio, C 2 -C 8  alkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkenyl, C 2 -C 8 haloalkynyl, aryl C 1 -C 8 alkyl or CO—X—CO 2 R 12 , in which X is selected from (CHR 12 )n, CR 12 ═CR 13  or C 6 H 4 , n=1-6; 
     R 2  and R 6  may be the same or different, respectively selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 3  and R 5  may be the same or different, respectively selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8  alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8  alkoxycarbonyloxy, C 1 -C 8 alkylaminocarbonyloxy, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8  alkoxyC 1 -C 8  alkoxy, C 1 -C 8 halo alkoxyC 1 -C 8 halo alkoxy, C 1 -C 8  alkoxycarbonylC 1 -C 8  alkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 4  is selected from H, halogen, CN, NO 2 , COOH, CO 2 Na, CO 2 NH 4 , C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8 alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkoxyC 1 -C 8  alkoxy, C 1 -C 8 haloalkoxyC 1 -C 8 haloalkoxy, SO 2 NR 12 R 13 , or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 7  is selected from Cl or CH 3 ; 
     R 8  is selected from H, halogen, OH, CN, NO 2 , COOH, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 1 -C 8 alkylsulfonyl, C 3 -C 8  cycloalkyl, C 2 -C 8 dialkylamino, C 3 -C 8  alkenyloxy, C 3 -C 8 haloalkenyloxy, C 3 -C 8 alkynyloxy, C 3 -C 8 halo alkynyloxy, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8 alkylcarbonylamino, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8  alkoxyC 1 -C 8  alkoxy, C 1 -C 8  alkoxycarbonylC 1 -C 8  alkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryloxy, arylamino, arylmethoxy, arylmethylamino, heteroaryloxy or heteroarylamino, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 9  is selected from H, halogen, NO 2 , CN, C(═O)NR 12 R 13 , C(═S)NR 12 R 13 , C 1 -C 8 alkylaminocarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8 haloalkyl or C 1 -C 8 alkylsulfonyl; 
     R 10  is selected from H, halogen, OH, CN, NO 2 , COOH, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 1 -C 8 alkylsulfonyl, C 2 -C 8 dialkylamino, C 3 -C 8 alkenyloxy, C 3 -C 8 haloalkenyloxy, C 3 -C 8  alkynyloxy, C 3 -C 8 halo alkynyloxy, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8 alkylcarbonylamino, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 alkoxyC 1 -C 8  alkoxy or C 1 -C 8  alkoxycarbonylC 1 -C 8 alkoxy; 
     R 11  is selected from CN or NO 2 , 
     R 12  and R 13  may be the same or different, respectively selected from H, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl; 
     R 14  is selected from halogen, NO 2 , CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 3 -C 6 alkenyloxy, C 3 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkylamino, C 1 -C 6 haloalkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarbonylamino, C 1 -C 6 haloalkylcarbonylamino, C 1 -C 6 alkylaminocarbonyl or C 1 -C 6 haloalkylaminocarbonyl; 
     Or the salts of the compounds having general formula I. 
     Furthermore, the preferred uses as antitumor compounds of general formula I of this invention include two kinds of compounds: 
     The first kind of compound is: R 7  is Cl, R 9  and R 11  are CN in compounds of general formula I, the structures are as general formula II: 
     
       
                 
         
             
             
         
      
     
     Wherein: 
     R 1  is selected from H, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 halo alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8 alkylamino carbonyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxyC 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 2 -C 8 haloalkenyl, C 2 -C 8 haloalkynyl, aryl C 1 -C 8 alkyl or CO—X—CO 2 R 12 , in which X is selected from (CHR 12 )n, CR 12 ═CR 13  or C 6 H 4 , n=1-6; 
     R 2  and R 6  may be the same or different, respectively selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 3  and R 5  may be the same or different, respectively selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8  alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8  alkoxycarbonyloxy, C 1 -C 8 alkylaminocarbonyloxy, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8  alkoxyC 1 -C 8  alkoxy, C 1 -C 8 haloalkoxyC 1 -C 8 haloalkoxy, C 1 -C 8  alkoxycarbonylC 1 -C 8  alkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 4  is selected from H, halogen, CN, NO 2 , COOH, CO 2 Na, CO 2 NH 4 , C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8 alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkoxyC 1 -C 8  alkoxy, C 1 -C 8 haloalkoxyC 1 -C 8 haloalkoxy, SO 2 NR 12 R 13 , or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl or arylaminocarbonyl, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 8  and R 10  may be the same or different, respectively selected from H, halogen, OH, CN, NO 2 , COOH, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkoxy, C 1 -C 8 haloalkoxy, C 1 -C 8 alkylamino, C 1 -C 8 haloalkylamino, C 1 -C 8 alkylthio, C 1 -C 8 haloalkylthio, C 1 -C 8 alkylsulfonyl, C 2 -C 8 dialkylamino, C 3 -C 8 alkenyloxy, C 3 -C 8 haloalkenyloxy, C 3 -C 8  alkynyloxy, C 3 -C 8 haloalkynyloxy, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8 alkylcarbonylamino, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8  alkoxyC 1 -C 8  alkoxy or C 1 -C 8 alkoxycarbonylC 1 -C 8  alkoxy; 
     R 12  and R 13  may be the same or different, respectively selected from H, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl; 
     R 14  is selected from halogen, NO 2 , CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halo alkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylcarbonyl, C 1 -C 6  alkoxycarbonyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 3 -C 6 alkenyloxy, C 3 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkylamino, C 1 -C 6 halo alkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarbonylamino, C 1 -C 6 halo alkylcarbonylamino, C 1 -C 6 alkylamino carbonyl or C 1 -C 6 halo alkylamino carbonyl; 
     Or the salts of the compounds having general formula II. 
     The preferred uses as antitumor compounds of general formula II of this invention are: 
     R 1  is selected from H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 halo alkylcarbonyl, C 1 -C 4  alkoxycarbonyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4  alkoxyC 1 -C 4 alkyl, C 1 -C 4 alkoxyC 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonylC 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, benzyl, phenethyl or CO—X—CO 2 R 12 , in which X is selected from (CHR 12 )n, CR 12 ═CR 13  or C 6 H 4 , n=1-3; 
     R 2  and R 6  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 halo alkyl, C 1 -C 4 alkoxy, C 1 -C 4 halo alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 halo alkylthio, C 2 -C 4  alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxyC 1 -C 4 alkyl, C 1 -C 4 alkoxycarbonylC 1 -C 4 alkyl, or the following groups unsubstituted or substituted with 1-3 R 14 : phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 3  and R 5  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylamino, C 1 -C 4 halo alkylamino, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4  alkoxycarbonyl, C 1 -C 4  alkoxyC 1 -C 4 alkyl, C 1 -C 4 alkoxycarbonylC 1 -C 4 alkyl, or the following groups unsubstituted or substituted with 1-3 R 14 : phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 4  is selected from H, Cl, Br, F, CN, NO 2 , COOH, CO 2 Na, CO 2 NH 4 , C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4  alkoxycarbonyl, C 1 -C 4 alkoxyC 1 -C 4 alkyl, C 1 -C 4  alkoxycarbonylC 1 -C 4 alkyl, C 1 -C 4 alkoxyC 1 -C 4 alkoxy, SO 2 NHCH 3 , SO 2 N(CH 3 ) 2 , or the following groups unsubstituted or substituted with 1-3 R 14 : phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl or phenylaminocarbonyl, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 8  and R 10  may be the same or different, respectively selected from Cl, Br, F, OH, CN, NO 2 , C 1 -C 4 alkyl, C 1 -C 4 halo alkyl, C 1 -C 4  alkoxy, C 1 -C 4 halo alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 halo alkylamino, C 1 -C 4 alkylthio, C 1 -C 4 halo alkylthio, C 1 -C 4 alkylsulfonyl, C 2 -C 6 dialkylamino, C 3 -C 4  alkenyloxy, C 3 -C 4 haloalkenyloxy, C 3 -C 4 alkynyloxy, C 3 -C 4 haloalkynyloxy, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonylamino, C 1 -C 4 alkylsulfonyloxy, C 1 -C 4  alkoxyC 1 -C 4 alkoxy or C 1 -C 4 alkoxycarbonylC 1 -C 4  alkoxy; 
     R 12  and R 13  may be the same or different, respectively selected from H or C 1 -C 4 alkyl; R 14  is selected from F, Cl, Br, NO 2 , CN, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 halo alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylcarbonyl, C 1 -C 4  alkoxycarbonyl or C 1 -C 4 alkylaminocarbonyl; 
     Or the salts of the compounds having general formula II. 
     Furthermore, the preferred uses as antitumor compounds of general formula II of this invention are: 
     R 1  is selected from H, CH 3 , acetyl, methylsulfonyl, benzyl or phenethyl; 
     R 2  and R 6  may be the same or different, respectively selected from H, F, Cl, Br, CN, NO 2 , COOH, CONH 2 , CONHCH 3 , CON(CH 3 ) 2 , CONHCH(CH 3 ) 2 , CONHC(CH 3 ) 3 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , C(CH 3 ) 3 , ClCH 2 , CF 3 , CH 3 O, C 2 H 5 O, CF 3 O, CF 3 CH 2 O, CH 3 S, CH 3 OCO or CH 3 OCH 2 ; 
     R 3  and R 5  may be the same or different, respectively selected from H, F, Cl, Br, CN, NO 2 , COOH, CONH 2 , CONHCH 3 , CON(CH 3 ) 2 , CONHCH(CH 3 ) 2 , CONHC(CH 3 ) 3 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , C(CH 3 ) 3 , ClCH 2 , CF 3 , CH 3 O, C 2 H 5 O, CF 3 O, CF 3 CH 2 O, CH 3 S, CH 3 OCO or CH 3 OCH 2 ; 
     R 4  is selected from H, F, Cl, Br, CN, NO 2 , COOH, CO 2 Na, CO 2 NH 4 , CONH 2 , CONHCH 3 , CON(CH 3 ) 2 , CONHCH(CH 3 ) 2 , CONHC(CH 3 ) 3 , CF 3 , CF 3 O, CH 3 OCO, C 2 H 5 OCO, CH 3 SO 2 , SO 2 NHCH 3 , SO 2 N(CH 3 ) 2 , phenoxycarbonyl, phenylaminocarbonyl, 4-CH 3 -phenylaminocarbonyl or 4-Cl-phenylaminocarbonyl; 
     R 8  and R 10  may be the same or different, respectively selected from Cl, F, CH 3 O, CF 3 O, CF 3 CH 2 O, CH 3 NH, (CH 3 ) 2 N, (C 2 H 5 ) 2 N, CF 3 CH 2 NH, ClCH 2 CH 2 NH, CH 3 S, C 2 H 5 S, CH 3 SO 2 , C 2 H 5 SO 2 , (CH 3 ) 2 N, CH 2 ═CHCH 2 O, C≡CCH 2 O, ClC≡CCH 2 O, IC≡CCH 2 O, CH 3 CO 2 , CH 3 CONH, CH 3 OCH 2 CH 2 O, C 2 H 5 OCH 2 CH 2 O, CH 3 OC(═O)CH 2 O or CH 3 OC(═O)CH 2 CH 2 O; 
     Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     Even more preferred uses as antitumor compounds of general formula II of this invention are: 
     R 1  is selected from H; 
     R 2  is selected from H, F, Cl, Br, CH 3 , C 2 H 5 , NO 2  or CN; 
     R 3  is selected from H, F, Cl, Br, CH 3  or CF 3 ; 
     R 4  is selected from H, F, Cl, Br, CF 3 , CF 3 O, CH 3 OCO, CN, NO 2 , COOH, CO 2 Na, phenylaminocarbonyl or 4-Cl-phenylaminocarbonyl; 
     R 5  is selected from H, Cl, Br, CH 3  or CF 3 ; 
     R 6  is selected from H, F, Cl, Br, CH 3 , C 2 H 5 , NO 2  or CN; 
     R 8  is selected from Cl, CH 3 O, CH 3 NH, (CH 3 ) 2 N or (C 2 H 5 ) 2 N; 
     R 10  is selected from Cl, CH 3 O or CH 3 NH; 
     Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     The more preferred uses as antitumor compounds of general formula II of this invention are: 
     R 1 , R 3  and R 5  are selected from H; 
     R 2  and R 6  are selected from H, Cl or Br; 
     R 4  is selected from H, Cl, Br, NO 2 , CF 3 , CF 3 O or CH 3 OCO; 
     R 8  and R 10  are selected from Cl; 
     Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     The most preferred uses as antitumor compounds of general formula II of this invention are: 
     
       
                 
         
             
             
         
      
       
                 
         
             
             
         
       
     
     The following structure in the most preferred uses as antitumor compounds of general formula II of this invention has never been reported before (refer to compound Table 6-112): 
     
       
                 
         
             
             
         
      
     
     The second kind of compound of the preferred uses as antitumor compounds of general formula I of this invention is: R 7  is CH 3 , R 10  is H, R 11  is NO 2 , the structures are as general formula III: 
     
       
                 
         
             
             
         
      
     
     Wherein: 
     R 1  is selected from H, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 halo alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8 alkylamino carbonyl, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 1 -C 8 alkylsulfonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxyC 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkylaminothio, C 2 -C 8 dialkylaminothio or CO—X—CO 2 R 12 , in which X is selected from (CHR 12 )n, CR 12 ═CR 13  or C 6 H 4 , n=1-6; 
     R 2  and R 6  may be the same or different, respectively selected from H, halogen, CN, NO 2 , C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkoxy, C 1 -C 8 haloalkoxy, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8 alkoxyC 1 -C 8 alkyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 3  and R 5  may be the same or different, respectively selected from H, halogen, CN, NO 2 , C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 halo alkyl, C 1 -C 8  alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8 alkoxycarbonyloxy, C 1 -C 8 alkylaminocarbonyloxy, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8 alkoxyC 1 -C 8 alkoxy, C 1 -C 8 halo alkoxyC 1 -C 8 halo alkoxy, C 1 -C 8  alkoxycarbonylC 1 -C 8  alkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 4  is selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 8 alkoxy, C 1 -C 8 halo alkoxy, C 2 -C 8 alkenyl, C 2 -C 8  alkynyl, C 1 -C 8 alkylsulfonyl, C 1 -C 8 alkylcarbonyl, C 1 -C 8 alkoxycarbonyl, C 1 -C 8  alkoxyC 1 -C 8 alkyl, C 1 -C 8  alkoxycarbonylC 1 -C 8 alkyl, C 1 -C 8 alkoxyC 1 -C 8  alkoxy, C 1 -C 8 haloalkoxyC 1 -C 8 haloalkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 8  is selected from H, halogen, C 1 -C 8 halo alkyl, C 1 -C 8  alkoxy, C 1 -C 8 halo alkoxy, C 1 -C 8 alkylamino, C 1 -C 8 halo alkylamino, C 1 -C 8 alkylthio, C 1 -C 8 halo alkylthio, C 1 -C 8 alkylsulfonyl, C 3 -C 8  cyclo alkyl, C 2 -C 8 dialkylamino, C 3 -C 8  alkenyloxy, C 3 -C 8 haloalkenyloxy, C 3 -C 8 alkynyloxy, C 3 -C 8 haloalkynyloxy, C 1 -C 8 alkylcarbonyloxy, C 1 -C 8 alkylcarbonylamino, C 1 -C 8 alkylsulfonyloxy, C 1 -C 8  alkoxyC 1 -C 8  alkoxy, C 1 -C 8 alkoxycarbonylC 1 -C 8 alkoxy, or the following groups unsubstituted or substituted with 1-5 R 14 : aryloxy, arylamino, arylmethoxy, arylmethylamino, heteroaryloxy or heteroarylamino, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 9  is selected from H, halogen, NO 2 , CN, C(═O)NR 12 R 13 , C(═S)NR 12 R 13 , C 1 -C 8 alkylamino carbonyl, C 1 -C 8  alkoxycarbonyl, C 1 -C 8 halo alkyl or C 1 -C 8 alkylsulfonyl; 
     R 12  and R 13  may be the same or different, respectively selected from H or C 1 -C 6 alkyl; 
     R 14  is selected from halogen, NO 2 , CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 3 -C 6 alkenyloxy, C 3 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkylamino, C 1 -C 6 halo alkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarbonylamino, C 1 -C 6 halo alkylcarbonylamino, C 1 -C 6 alkylaminocarbonyl or C 1 -C 6 haloalkylaminocarbonyl; 
     Or the salts of the compounds having general formula III. 
     The preferred uses as antitumor compounds of general formula III of this invention are: 
     R 1  is selected from H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 haloalkylcarbonyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylthio, C 1 -C 4 halo alkylthio, C 1 -C 4 alkylsulfonyl, C 1 -C 4  alkoxyC 1 -C 4 alkyl, C 1 -C 4 alkoxyC 1 -C 4 alkylcarbonyl, C 1 -C 4  alkoxycarbonylC 1 -C 4 alkyl, C 1 -C 4 alkylaminothio, C 2 -C 4 dialkylaminothio or CO—X—CO 2 R 12 , in which X is selected from (CHR 12 )n, CR 12 ═CR 13  or C 6 H 4 , n=1-3; 
     R 2  and R 6  may be the same or different, respectively selected from H, halogen, CN, NO 2 , C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxyC 1 -C 4 alkyl, C 1 -C 4 alkoxycarbonylC 1 -C 4 alkyl, or the following groups unsubstituted or substituted with 1-4 R 14 : phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 3  and R 5  may be the same or different, respectively selected from H, halogen, CN, NO 2 , C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 halo alkyl, C 1 -C 4  alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylamino, C 1 -C 4 haloalkylamino, C 1 -C 4 alkylthio, C 1 -C 4 halo alkylthio, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl or C 1 -C 4  alkoxyC 1 -C 4 alkyl; 
     R 4  is selected from H, halogen, CN, NO 2 , COOH, C(═O)NR 12 R 13 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 halo alkoxy, C 2 -C 6 alkenyl, C 2 -C 6  alkynyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4  alkoxyC 1 -C 4 alkyl, C 1 -C 4  alkoxycarbonylC 1 -C 4 alkyl, C 1 -C 4 alkoxyC 1 -C 4 alkoxy, or the following groups unsubstituted or substituted with 1-4 R 14 : phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 8  is selected from H, halogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylamino, C 1 -C 4 haloalkylamino, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylsulfonyl, C 2 -C 4 dialkylamino, C 3 -C 4 alkenyloxy, C 3 -C 4 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 1 -C 4 alkylcarbonyloxy, C 1 -C 4 alkylcarbonylamino, C 1 -C 4 alkylsulfonyloxy, C 1 -C 4  alkoxyC 1 -C 4 alkoxy, C 1 -C 4 alkoxycarbonylC 1 -C 4 alkoxy, or the following groups unsubstituted or substituted with 1-3 R 14 : phenoxy, phenylamino, benzyloxy, benzylamino, pyridyloxy or pyridylamino, and when the number of the substitutes is more than 1, R 14  may be the same or different; 
     R 9  is selected from Cl, Br, F, NO 2 , CN, C(═O)NR 12 R 13 , C(═S)NR 12 R 13 , CO 2 CH 3 , CF 3  or CH 3 SO 2 ; 
     R 12  and R 13  may be the same or different, respectively selected from H or C 1 -C 3 alkyl; 
     R 14  is selected from halogen, NO 2 , CN, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 1 -C 3 alkylthio, C 1 -C 3 alkylcarbonyl, C 1 -C 3  alkoxycarbonyl, C 1 -C 3 alkylamino, C 2 -C 4 dialkylamino, C 1 -C 3 alkylcarbonylamino or C 1 -C 3 alkylaminocarbonyl; 
     Or the salts of the compounds having general formula III. 
     Furthermore, the preferred uses as antitumor compounds of general formula III of this invention are: 
     R 1  is selected from H, CH 3 , C 2 H 5 , cyclopropyl, formyl, acetyl, COCF 3 , CO 2 CH 3 , CO 2 C 2 H 5 , SCCl 3 , SO 2 CH 3 , SO 2 C 2 H 5 , CH 2 OCH 3 , CH 2 OC 2 H 5 , CH 2 CH 2 OCH 3 , COCH 2 OCH 3 , CH 2 COOCH 3 , SNHCH 3 , SN(CH 3 ) 2 , COCH 2 CO 2 H, COCH 2 CO 2 CH 3 , COCH 2 CH 2 CO 2 H, COCH 2 CH 2 CO 2 CH 3 , COCHCH 3 CO 2 H, COCHCH 3 CO 2 CH 3 , COC 6 H 4 CO 2 H, COC 6 H 4 CO 2 CH 3 , COCH═CHCO 2 H or COCH═CHCO 2 CH 3 ; 
     R 2  and R 6  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , C(═O)NH 2 , C(═O)NHCH 3 , C(═O)N(CH 3 ) 2 , CH 3 , C 2 H 5 , CF 3 , OCH 3 , OC 2 H 5 , OCF 3 , SO 2 CH 3 , SO 2 C 2 H 5 , COCH 3 , CO 2 CH 3 , CO 2 C 2 H 5 , phenoxy, phenylamino, phenoxycarbonyl or phenylaminocarbonyl; 
     R 3  and R 5  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , C(═O)NH 2 , CH 3 , CF 3 , OCH 3 , OCF 3 , NHCH 3 , SCH 3 , SO 2 CH 3 , SO 2 C 2 H 5 , COCH 3 , CO 2 CH 3 , CO 2 C 2 H 5  or CH 2 OCH 3 ; 
     R 4  is selected from H, Cl, Br, F, CN, NO 2 , CO 2 H, C(═O)NH 2 , C(═O)NHCH 3 , C(═O)N(CH 3 ) 2 , CH 3 , CF 3 , CF(CF 3 ) 2 , OCF 3 , OCH 2 CF 3 , OCF 2 CHFCF 3 , SO 2 CH 3 , SO 2 C 2 H 5 , COCH 3 , CO 2 CH 3 , CO 2 C 2 H 5 , phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, pyridyloxy or 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy; 
     R 8  is selected from H, Cl, Br, F, C 1 -C 3  alkoxy, C 1 -C 3  haloalkoxy, C 1 -C 3 alkylamino, C 1 -C 3 haloalkylamino, SCH 3 , SC 2 H 5 , N(CH 3 ) 2 , N(C 2 H 5 ) 2 , OCH 2 OCH 3 , phenoxy, phenylamino, benzyloxy, benzylamino, 4-chlorophenoxy, 4-chlorophenylamino, 2-chloro-4-(trifluoromethyl)phenoxy, 2-chloro-4-(trifluoromethyl)phenylamino, 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy or 3-chloro-5-(trifluoromethyl)pyridin-2-ylamino; 
     R 9  is NO 2 ; 
     Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     Even more preferred uses as antitumor compounds of general formula III of this invention are: 
     R 1  is selected from H or CH 3 ; 
     R 2  and R 6  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , C(═O)NH 2 , C(═O)NHCH 3 , C(═O)N(CH 3 ) 2 , CH 3 , CF 3 , CO 2 CH 3  or phenoxycarbonyl; 
     R 3  and R 5  may be the same or different, respectively selected from H, Cl, Br, F, CN, NO 2 , CH 3 , CF 3  or OCH 3 ; 
     R 4  is selected from H, Cl, Br, F, CN, NO 2 , CO 2 H, C(═O)NH 2 , C(═O)NHCH 3 , CH 3 , CF 3 , OCF 2 CHFCF 3 , CO 2 CH 3  or 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy; 
     R 8  is selected from H, Cl, OCH 3 , OCH 2 CF 3 , NHCH 3 , SCH 3  or N(CH 3 ) 2 ; 
     R 9  is NO 2 , 
     Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     The more preferred uses as antitumor compounds of general formula III of this invention are: 
     R 1 , R 3  and R 5  are selected from H; 
     R 2  is selected from Cl or F; 
     R 4  is selected from H, Cl, CN, NO 2  or CF 3 ; 
     R 6  is selected from F, Cl, CN or NO 2 ; 
     R 8  is selected from H, Cl or OCH 2 CF 3 ; 
     R 9  is NO 2 , 
     Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid. 
     The most preferred uses as antitumor compounds of general formula III of this invention are: 
     
       
                 
         
             
             
         
      
       
                 
         
             
             
         
       
     
     The terms used above to definite the compounds of general formula I represent substitutes as follow: 
     The “halogen” or “halo” is fluorine, chlorine, bromine or iodine. 
     The “alkyl” stands for straight or branched chain alkyl, such as methyl, ethyl, propyl, isopropyl or tert-butyl. 
     The “cycloalkyl” is substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl. The substitute(s) is(are) methyl, halogen, etc. 
     The “haloalkyl” stands for straight or branched chain alkyl, in which hydrogen atoms can be all or partly substituted with halogen, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. 
     The “alkoxy” refers to straight or branched chain alkyl, which is linked to the structure by oxygen atom. 
     The “haloalkoxy” refers to straight or branched chain alkoxy, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc. 
     The “alkylthio” refers to straight or branched chain alkyl, which is linked to the structure by sulfur atom. 
     The “haloalkylthio” refers to straight or branched chain alkylthio, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, etc. 
     The “alkylamino” refers to straight or branched chain alkyl, which is linked to the structure by nitrogen atom. 
     The “haloalkylamino” refers to straight or branched chain alkylamino, in which hydrogen atoms may be all or partly substituted with halogen. 
     The “alkenyl” refers to straight or branched chain alkenyl, such as ethenyl, 1-propenyl, 2-propenyl and different isomer of butenyl, pentenyl and hexenyl. Alkenyl also includes polyene, such as propa-1,2-dienyl and hexa-2,4-dienyl. 
     The “haloalkenyl” stands for straight or branched chain alkenyl, in which hydrogen atoms can be all or partly substituted with halogen. 
     The “alkynyl” refers to straight or branched chain alkynyl, such as ethynyl, 1-propynyl, 2-propynyl and different isomer of butynyl, pentynyl and hexynyl. Alkynyl also includes groups including more than one triple bonds, such as hexa-2,5-diynyl. 
     The “haloalkynyl” stands for straight or branched chain alkynyl, in which hydrogen atoms can be all or partly substituted with halogen. 
     The alkenyloxy refers to straight or branched chain alkenyl, which is linked to the structure by oxygen atom. 
     The alkynyloxy refers to straight or branched chain alkynyl, which is linked to the structure by oxygen atom. 
     The alkylsulfonyl refers to straight or branched chain alkyl, which is linked to the structure by sulfuryl(—SO 2 —), such as SO 2 CH 3 . 
     The alkylcarbonyl refers to straight or branched chain alkyl, which is linked to the structure by carbonyl(—CO—), such as CH 3 CO—, CH 3 CH 2 CO—. 
     The alkylcarbonyloxy: such as CH 3 COO—, CH 3 CH 2 NHCOO—. 
     The alkylcarbonylamino: such as CH 3 CONH—, CH 3 CH 2 NHCONH—. 
     The alkylsulfonyloxy: such as alkyl-S(O) 2 —O—. 
     The alkoxycarbonyl: alkyl-O—CO—. 
     The phenylaminocarbonyl: phenyl-NH—CO—. 
     The aryl in aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl and arylaminocarbonyl refers to phenyl or naphthyl, etc. 
     The “heteroaryl” stands for five member ring or six member ring containing one or more N, O, S hetero atoms. Such as furanyl, pyrazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, etc. 
     Part of the substitutes of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8  and R 10  in formula I are separately listed in table 1, table 2, table 3, table 4 and table 5, but without being restricted thereby. 
     
       
                 
         
             
             
         
      
     
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 substitute R 1   
               
             
          
           
               
                   
                 R 1   
                 R 1   
                 R 1   
               
               
                   
               
               
                   
                 H 
                 CO 2 CH 3   
                 CH 2 C≡C—Cl 
               
               
                   
                 CH 3   
                 CO 2 CH 2 CH 3   
                 CH 2 C≡CCH 3   
               
               
                   
                 C 2 H 5   
                 SO 2 CH 2 CH 3   
                 PhCH 2   
               
               
                   
                 n-C 3 H 7   
                 CH 2 OCH 3   
                 PhCH 2 CH 2   
               
               
                   
                 i-C 3 H 7   
                 CH 2 CH 2 OCH 3   
                 4-Cl—PhCH 2   
               
               
                   
                 n-C 4 H 9   
                 CH 2 CH 2 OCH 2 CH 3   
                 COCH 2 CO 2 CH 3   
               
               
                   
                 t-C 4 H 9   
                 COCH 2 OCH 3   
                 COCH 2 CH 2 CO 2 CH 3   
               
               
                   
               
               
                   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 COCH 2 OCH 2 CH 3   
                 COCHCH 3 CO 2 CH 3   
               
               
                   
               
               
                   
                 CH 2 Cl 
                 CH 2 CO 2 CH 3   
                 COCH 2 COOH 
               
               
                   
                 CF 3   
                 CH 2 CO 2 CH 2 CH 3   
                 COCH 2 CH 2 COOH 
               
               
                   
                 CH 2 CF 3   
                 CH 2 CH═CH 2   
                 COCHCH 3 COOH 
               
               
                   
                 COCH 3   
                 CH 2 CH═CF 2   
                 COCH═CHCOOH 
               
               
                   
                 COCH 2 CH 3   
                 CH 2 CH 2 CH═CF 2   
                 COCH═CHCO 2 CH 3   
               
               
                   
               
               
                   
                 COCH 2 CH 2 CH 3  CONHCH 3   
                 CH 2 CH 2 CF═CF 2  CH 2 CH═CCl 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 CONHCH 2 CH 3  SO 2 CH 3   
                 CH 2 C≡CH CH 2 C≡C—I 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 substitute R 2 (R 6 ) 
               
             
          
           
               
                 R 2 (R 6 ) 
                 R 2 (R 6 ) 
                 R 2 (R 6 ) 
                 R 2 (R 6 ) 
               
               
                   
               
               
                 H 
                 CH 3   
                 OCH(CH 3 ) 2   
                 CH 2 CO 2 CH 2 CH 3   
               
               
                 F 
                 CH 2 CH 3   
                 OCF 3   
                 Ph 
               
               
                 Cl 
                 n-C 3 H 7   
                 OCH 2 CF 3   
                 CH 2 Ph 
               
               
                 Br 
                 i-C 3 H 7   
                 OCF 2 CF 3   
                 OPh 
               
               
                 I 
                 n-C 4 H 9   
                 CH═CH 2   
                 NHPh 
               
               
                 CN 
                 t-C 4 H 9   
                 CH 2 CH═CH 2   
                 COPh 
               
               
                 NO 2   
                 CF 3   
                 C≡CH 
                 CO 2 Ph 
               
               
                 COOH 
                 CHF 2   
                 CH 2 C≡CH 
                 CO 2 Ph-4-Cl 
               
               
                 CONH 2   
                 CH 2 F 
                 SO 2 CH 3   
                 CO 2 Ph-2-Cl-4-CF 3   
               
               
                 CONHCH 3   
                 CH 2 Cl 
                 SO 2 CH 2 CH 3   
                 CO 2 Ph-2-Cl-4-NO 2   
               
               
                 CON(CH 3 ) 2   
                 CH 2 Br 
                 COCH 3   
                 CONHPh 
               
               
                 CONHCH 2 CH 3   
                 CH 2 CF 3   
                 COCH 2 CH 3   
                 CONHPh-4-Cl 
               
               
                 CON(CH 2 CH 3 ) 2   
                 CF 2 CHF 2   
                 CO 2 CH 3   
                 CONHPh-2-Cl 
               
               
                 CONH(CH 2 ) 2 CH 3   
                 CF 2 CF 3   
                 CO 2 CH 2 CH 3   
                 CONHPh-4-NO 2   
               
               
                 CONHCH(CH 3 ) 2   
                 OCH 3   
                 CH 2 OCH 3   
                 CONHPh-2-Cl-4-CF 3   
               
               
                 CONH(CH 2 ) 3 CH 3   
                 OCH 2 CH 3   
                 CH 2 OCH 2 CH 3   
                 CONHPh-2-Cl-4-NO 2   
               
               
                   
               
               
                 CONHC(CH 3 ) 3   
                 O(CH 2 ) 2 CH 3   
                 CH 2 CO 2 CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 substitute R 3 (R 5 ) 
               
             
          
           
               
                 R 3 (R 5 ) 
                 R 3 (R 5 ) 
                 R 3 (R 5 ) 
                 R 3 (R 5 ) 
               
               
                   
               
               
                 H 
                 n-C 3 H 7   
                 OCH 2 CF 3   
                 CH 2 Ph 
               
               
                 F 
                 i-C 3 H 7   
                 OCF 2 CF 3   
                 OPh 
               
               
                 Cl 
                 n-C 4 H 9   
                 CH═CH 2   
                 NHPh 
               
               
                 Br 
                 t-C 4 H 9   
                 CH 2 CH═CH 2   
                 COPh 
               
               
                 I 
                 CF 3   
                 C≡CH 
                 CO 2 Ph 
               
               
                 CN 
                 CHF 2   
                 CH 2 C≡CH 
                 CO 2 Ph-4-Cl 
               
               
                 NO 2   
                 CH 2 F 
                 SO 2 CH 3   
                 CO 2 Ph-2-Cl-4-CF 3   
               
               
                 COOH 
                 CH 2 Cl 
                 SO 2 CH 2 CH 3   
                 CO 2 Ph-2-Cl-4-NO 2   
               
               
                 CONH 2   
                 CH 2 Br 
                 COCH 3   
                 CONHPh 
               
               
                 CONHCH 3   
                 CH 2 CF 3   
                 COCH 2 CH 3   
                 CONHPh-4-Cl 
               
               
                 CON(CH 3 ) 2   
                 CF 2 CHF 2   
                 CO 2 CH 3   
                 CONHPh-2-Cl 
               
               
                 CONHCH 2 CH 3   
                 CF 2 CF 3   
                 CO 2 CH 2 CH 3   
                 CONHPh-4-NO 2   
               
               
                 CON(CH 2 CH 3 ) 2   
                 OCH 3   
                 CH 2 OCH 3   
                 CONHPh-2-Cl-4-CF 3   
               
               
                 CONH(CH 2 ) 2 CH 3   
                 OCH 2 CH 3   
                 CH 2 OCH 2 CH 3   
                 CONHPh-2-Cl-4-NO 2   
               
               
                   
               
               
                 CONHCH(CH 3 ) 2  CH 3  CH 2 CH 3   
                 O(CH 2 ) 2 CH 3  OCH(CH 3 ) 2  OCF 3   
                 CH 2 CO 2 CH 3  CH 2 CO 2 CH 2 CH 3  Ph 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 substitute R 4   
               
             
          
           
               
                 R 4   
                 R 4   
                 R 4   
                 R 4   
               
               
                   
               
               
                 H 
                 CHF 2   
                 CH 2 C≡CH 
                 CONHCH(CH 3 ) 2   
               
               
                 F 
                 CH 2 F 
                 SO 2 CH 3   
                 CON(CH 2 CH 3 ) 2   
               
               
                 Cl 
                 CH 2 Cl 
                 SO 2 CH 2 CH 3   
                 CONHC(CH 3 ) 3   
               
               
                 Br 
                 CH 2 Br 
                 COCH 3   
                 SO 2 NH 2   
               
               
                 I 
                 CH 2 CF 3   
                 COCH 2 CH 3   
                 SO 2 NHCH 3   
               
               
                 CN 
                 CF 2 CHF 2   
                 CO 2 CH 3   
                 SO 2 N(CH 3 ) 2   
               
               
                 NO 2   
                 CF 2 CF 3   
                 CO 2 CH 2 CH 3   
                 Ph 
               
               
                 COOH 
                 OCH 3   
                 CH 2 OCH 3   
                 CH 2 Ph 
               
               
                 CO 2 Na 
                 OCH 2 CH 3   
                 CH 2 OCH 2 CH 3   
                 COPh 
               
               
                 CO 2 NH 4   
                 O(CH 2 ) 2 CH 3   
                 CH 2 CO 2 CH 3   
                 COCH 2 Ph 
               
               
                 CH 3   
                 OCH(CH 3 ) 2   
                 CH 2 CO 2 CH 2 CH 3   
                 CO 2 Ph 
               
               
                 CH 2 CH 3   
                 OCF 3   
                 OCH 2 OCH 3   
                 CO 2 Ph-2-Cl-4-CF 3   
               
               
                 n-C 3 H 7   
                 OCH 2 CF 3   
                 OCH 2 OCH 2 CH 3   
                 CONHPh 
               
               
                 i-C 3 H 7   
                 OCF 2 CF 3   
                 CONH 2   
                 CONHPh-4-Cl 
               
               
                 n-C 4 H 9   
                 CH═CH 2   
                 CONHCH 3   
                 CONHPh-4-CH 3   
               
               
                 t-C 4 H 9   
                 CH 2 CH═CH 2   
                 CON(CH 3 ) 2   
                 CONHPh-2-Cl-4-NO 2   
               
               
                 CF 3   
                 C≡CH 
                 CONH(CH 2 ) 2 CH 3   
                 CONHPh-2-Cl-4-CF 3   
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 substitute R 8 (R 10 ) 
               
             
          
           
               
                 R 8 (R 10 ) 
                 R 8 (R 10 ) 
                 R 8 (R 10 ) 
                 R 8 (R 10 ) 
                 R 8 (R 10 ) 
               
               
                   
               
               
                 H 
                 CH 3   
                 OCH 3   
                 SCH 3   
                 OCOCH 3   
               
               
                 F 
                 C 2 H 5   
                 OCH 2 CH 3   
                 SCH 2 CH 3   
                 OCOCH 2 CH 3   
               
               
                 Cl 
                 n-C 3 H 7   
                 OCF 3   
                 SO 2 CH 3   
                 NHCOCH 3   
               
               
                 Br 
                 i-C 3 H 7   
                 OCH 2 CF 3   
                 SO 2 CH 2 CH 3   
                 NHCOCH 2 CH 3   
               
               
                 I 
                 n-C 4 H 9   
                 NHCH 3   
                 N(CH 3 ) 2   
                 OSO 2 CH 3   
               
               
                 OH 
                 t-C 4 H 9   
                 NHCH 2 CH 3   
                 N(C 2 H 5 ) 2   
                 OSO 2 CH 2 CH 3   
               
               
                 CN 
                 CH 2 Cl 
                 NH(CH 2 ) 2 CH 3   
                 OCH 2 CH═CH 2   
                 OCH 2 OCH 3   
               
               
                 NO 2   
                 CF 3   
                 NHCH(CH 3 ) 2   
                 OCH 2 CH═CCl 2   
                 OCH 2 OCH 2 CH 3   
               
               
                 COOH 
                 CH 2 CF 3   
                 NHCH 2 CF 3   
                 OCH 2 C≡CH 
                 OCH 2 CO 2 CH 3   
               
               
                   
               
             
          
         
       
     
     The present invention is also explained by the following compounds having general formula II with antitumor activity in Table 6-Table 21, but without being restricted thereby. 
     
       
                 
         
             
             
         
      
     
     Table 6: In formula II, R 1  is H, R 8  and R 10  are Cl, R 2 , R 3 , R 4 , R 5  and R 6  (hereinafter abbreviated to R 2 -R 6 ) are listed in following Table, the numbers of representative compounds are Table 6-1 to Table 6-208. 
     
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
               
                   
               
               
                 Num- 
                   
                   
                   
                   
                   
               
               
                 ber 
                 R 2   
                 R 3   
                 R 4   
                 R 5   
                 R 6   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 H 
                 H 
                 H 
                 H 
                 H 
               
               
                 2 
                 F 
                 H 
                 H 
                 H 
                 H 
               
               
                 3 
                 Cl 
                 H 
                 H 
                 H 
                 H 
               
               
                 4 
                 Br 
                 H 
                 H 
                 H 
                 H 
               
               
                 5 
                 I 
                 H 
                 H 
                 H 
                 H 
               
               
                 6 
                 CH 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 7 
                 OCH 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 8 
                 NO 2   
                 H 
                 H 
                 H 
                 H 
               
               
                 9 
                 CF 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 10 
                 CN 
                 H 
                 H 
                 H 
                 H 
               
               
                 11 
                 H 
                 F 
                 H 
                 H 
                 H 
               
               
                 12 
                 H 
                 Cl 
                 H 
                 H 
                 H 
               
               
                 13 
                 H 
                 Br 
                 H 
                 H 
                 H 
               
               
                 14 
                 H 
                 CF 3   
                 H 
                 H 
                 H 
               
               
                 15 
                 H 
                 H 
                 F 
                 H 
                 H 
               
               
                 16 
                 H 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 17 
                 H 
                 H 
                 Br 
                 H 
                 H 
               
               
                 18 
                 H 
                 H 
                 CH 3   
                 H 
                 H 
               
               
                 19 
                 H 
                 H 
                 t-C 4 H 9   
                 H 
                 H 
               
               
                 20 
                 H 
                 H 
                 OCH 3   
                 H 
                 H 
               
               
                 21 
                 H 
                 H 
                 OCF 3   
                 H 
                 H 
               
               
                 22 
                 H 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 23 
                 H 
                 H 
                 CN 
                 H 
                 H 
               
               
                 24 
                 H 
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 25 
                 H 
                 H 
                 CO 2 CH 3   
                 H 
                 H 
               
               
                 26 
                 H 
                 H 
                 SO 2 CH 3   
                 H 
                 H 
               
               
                 27 
                 H 
                 H 
                 CONHPh 
                 H 
                 H 
               
               
                 28 
                 H 
                 H 
                 CONHPh-4-CH 3   
                 H 
                 H 
               
               
                 29 
                 H 
                 H 
                 CONHPh-4-Cl 
                 H 
                 H 
               
               
                 30 
                 F 
                 F 
                 H 
                 H 
                 H 
               
               
                 31 
                 F 
                 H 
                 F 
                 H 
                 H 
               
               
                 32 
                 F 
                 H 
                 H 
                 F 
                 H 
               
               
                 33 
                 F 
                 H 
                 H 
                 H 
                 F 
               
               
                 34 
                 F 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 35 
                 F 
                 H 
                 H 
                 CF 3   
                 H 
               
               
                 36 
                 H 
                 F 
                 F 
                 H 
                 H 
               
               
                 37 
                 H 
                 F 
                 H 
                 F 
                 H 
               
               
                 38 
                 Cl 
                 Cl 
                 H 
                 H 
                 H 
               
               
                 39 
                 Cl 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 40 
                 Cl 
                 H 
                 H 
                 Cl 
                 H 
               
               
                 41 
                 Cl 
                 H 
                 H 
                 H 
                 Cl 
               
               
                 42 
                 Cl 
                 H 
                 H 
                 H 
                 CH 3   
               
               
                 43 
                 H 
                 Cl 
                 Cl 
                 H 
                 H 
               
               
                 44 
                 H 
                 Cl 
                 H 
                 Cl 
                 H 
               
               
                 45 
                 Cl 
                 H 
                 Br 
                 H 
                 H 
               
               
                 46 
                 Br 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 47 
                 Cl 
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 48 
                 Cl 
                 H 
                 H 
                 CF 3   
                 H 
               
               
                 49 
                 Cl 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 50 
                 Cl 
                 H 
                 H 
                 NO 2   
                 H 
               
               
                 51 
                 Cl 
                 H 
                 H 
                 CN 
                 H 
               
               
                 52 
                 Cl 
                 H 
                 H 
                 CH 3   
                 H 
               
               
                 53 
                 NO 2   
                 H 
                 H 
                 Cl 
                 H 
               
               
                 54 
                 CN 
                 H 
                 H 
                 Cl 
                 H 
               
               
                 55 
                 CH 3   
                 H 
                 H 
                 Cl 
                 H 
               
               
                 56 
                 CF 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 57 
                 F 
                 H 
                 CN 
                 H 
                 H 
               
               
                 58 
                 Cl 
                 H 
                 CN 
                 H 
                 H 
               
               
                 59 
                 Br 
                 H 
                 CN 
                 H 
                 H 
               
               
                 60 
                 NO 2   
                 H 
                 CN 
                 H 
                 H 
               
               
                 61 
                 t-C 4 H 9   
                 H 
                 CN 
                 H 
                 H 
               
               
                 62 
                 OCH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 63 
                 CO 2 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 64 
                 SO 2 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 65 
                 H 
                 F 
                 CN 
                 H 
                 H 
               
               
                 66 
                 H 
                 Cl 
                 CN 
                 H 
                 H 
               
               
                 67 
                 H 
                 Br 
                 CN 
                 H 
                 H 
               
               
                 68 
                 H 
                 NO 2   
                 CN 
                 H 
                 H 
               
               
                 69 
                 H 
                 CH 3   
                 CN 
                 H 
                 H 
               
               
                 70 
                 H 
                 OCH 3   
                 CN 
                 H 
                 H 
               
               
                 71 
                 CN 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 72 
                 CF 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 73 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 74 
                 H 
                 CN 
                 Cl 
                 H 
                 H 
               
               
                 75 
                 H 
                 CH 3   
                 Cl 
                 H 
                 H 
               
               
                 76 
                 H 
                 CF 3   
                 Cl 
                 H 
                 H 
               
               
                 77 
                 CH 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 78 
                 CH 3   
                 Cl 
                 H 
                 H 
                 H 
               
               
                 79 
                 CH 3   
                 H 
                 CH 3   
                 H 
                 H 
               
               
                 80 
                 CH 3   
                 H 
                 H 
                 CH 3   
                 H 
               
               
                 81 
                 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 82 
                 CH 3   
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 83 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 H 
               
               
                 84 
                 CH 3   
                 H 
                 H 
                 H 
                 CO 2 CH 3   
               
               
                 85 
                 H 
                 CF 3   
                 CN 
                 H 
                 H 
               
               
                 86 
                 H 
                 CH 3   
                 CN 
                 H 
                 H 
               
               
                 87 
                 NO 2   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 88 
                 CN 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 89 
                 F 
                 F 
                 F 
                 H 
                 H 
               
               
                 90 
                 F 
                 H 
                 F 
                 H 
                 F 
               
               
                 91 
                 F 
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 92 
                 Cl 
                 Cl 
                 Cl 
                 H 
                 H 
               
               
                 93 
                 Cl 
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 94 
                 Cl 
                 Cl 
                 H 
                 Cl 
                 H 
               
               
                 95 
                 Cl 
                 H 
                 CF 3   
                 H 
                 Cl 
               
               
                 96 
                 Cl 
                 H 
                 OCF 3   
                 H 
                 Cl 
               
               
                 97 
                 Cl 
                 H 
                 CH 3   
                 H 
                 Cl 
               
               
                 98 
                 Cl 
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 99 
                 Cl 
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 100 
                 Cl 
                 H 
                 CO 2 CH 3   
                 H 
                 Cl 
               
               
                 101 
                 Cl 
                 H 
                 SO 2 CH 3   
                 H 
                 Cl 
               
               
                 102 
                 Cl 
                 H 
                 t-C 4 H 9   
                 H 
                 Cl 
               
               
                 103 
                 Cl 
                 H 
                 CONHPh 
                 H 
                 Cl 
               
               
                 104 
                 Cl 
                 H 
                 CONHPh-4-Cl 
                 H 
                 Cl 
               
               
                 105 
                 Cl 
                 H 
                 CO 2 Na 
                 H 
                 Cl 
               
               
                 106 
                 Cl 
                 H 
                 COOH 
                 H 
                 Cl 
               
               
                 107 
                 Cl 
                 H 
                 NO 2   
                 H 
                 CH 3   
               
               
                 108 
                 Cl 
                 CH 3   
                 Cl 
                 H 
                 H 
               
               
                 109 
                 Cl 
                 H 
                 Cl 
                 H 
                 CN 
               
               
                 110 
                 Cl 
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 111 
                 Br 
                 H 
                 OCF 3   
                 H 
                 Br 
               
               
                 112 
                 Br 
                 H 
                 Br 
                 H 
                 Br 
               
               
                 113 
                 Br 
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 114 
                 Br 
                 H 
                 NO 2   
                 H 
                 Br 
               
               
                 115 
                 CH 3   
                 H 
                 CH 3   
                 H 
                 CH 3   
               
               
                 116 
                 CH 3   
                 H 
                 t-C 4 H 9   
                 H 
                 CH 3   
               
               
                 117 
                 C 2 H 5   
                 H 
                 Cl 
                 H 
                 C 2 H 5   
               
               
                 118 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 Br 
               
               
                 119 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 NO 2   
               
               
                 120 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 CN 
               
               
                 121 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 OCH 3   
               
               
                 122 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 CF 3   
               
               
                 123 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 Cl 
               
               
                 124 
                 CH 3   
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 125 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 126 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 127 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 Br 
               
               
                 128 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 129 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CN 
               
               
                 130 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 OCH 3   
               
               
                 131 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CF 3   
               
               
                 132 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CO 2 CH 3   
               
               
                 133 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 SO 2 CH 3   
               
               
                 134 
                 C 2 H 5   
                 Cl 
                 H 
                 H 
                 C 2 H 5   
               
               
                 135 
                 Cl 
                 H 
                 CN 
                 H 
                 F 
               
               
                 136 
                 Cl 
                 H 
                 CN 
                 H 
                 Br 
               
               
                 137 
                 Cl 
                 H 
                 CN 
                 H 
                 NO 2   
               
               
                 138 
                 Cl 
                 H 
                 CN 
                 H 
                 OCH 3   
               
               
                 139 
                 Cl 
                 H 
                 CN 
                 H 
                 CO 2 CH 3   
               
               
                 140 
                 F 
                 H 
                 CN 
                 H 
                 Br 
               
               
                 141 
                 F 
                 H 
                 CN 
                 H 
                 NO 2   
               
               
                 142 
                 F 
                 H 
                 CN 
                 H 
                 OCH 3   
               
               
                 143 
                 F 
                 H 
                 CN 
                 H 
                 CO 2 CH 3   
               
               
                 144 
                 Cl 
                 H 
                 SO 2 NHCH 3   
                 H 
                 Cl 
               
               
                 145 
                 Cl 
                 H 
                 SO 2 N(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 146 
                 Cl 
                 H 
                 CO 2 NH 4   
                 H 
                 Cl 
               
               
                 147 
                 Cl 
                 H 
                 CONH 2   
                 H 
                 Cl 
               
               
                 148 
                 Cl 
                 H 
                 CONHCH 3   
                 H 
                 Cl 
               
               
                 149 
                 Cl 
                 H 
                 CON(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 150 
                 Cl 
                 H 
                 CONHCH(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 151 
                 Cl 
                 H 
                 CONHC(CH 3 ) 3   
                 H 
                 Cl 
               
               
                 152 
                 CH 3   
                 H 
                 Cl 
                 CH 3   
                 H 
               
               
                 153 
                 NO 2   
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 154 
                 CN 
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 155 
                 CN 
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 156 
                 CN 
                 H 
                 Cl 
                 H 
                 CN 
               
               
                 157 
                 CN 
                 H 
                 Cl 
                 H 
                 CF 3   
               
               
                 158 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 159 
                 CH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 160 
                 NO 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 161 
                 CF 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 162 
                 OCH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 163 
                 NO 2   
                 H 
                 Cl 
                 H 
                 F 
               
               
                 164 
                 NO 2   
                 H 
                 Cl 
                 H 
                 Br 
               
               
                 165 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CF 3   
               
               
                 166 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CO 2 CH 3   
               
               
                 167 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 168 
                 CN 
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 169 
                 COOH 
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 170 
                 COOH 
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 171 
                 COOH 
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 172 
                 COOH 
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 173 
                 COOH 
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 174 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 175 
                 CO 2 CH 3   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 176 
                 CONHCH 3   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 177 
                 CONHCH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 178 
                 CONHCH 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 179 
                 CONHCH 3   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 180 
                 CONHCH 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 181 
                 CONH 2   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 182 
                 CONH 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 183 
                 CONH 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 184 
                 CONH 2   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 185 
                 CONH 2   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 186 
                 CON(CH 3 ) 2   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 187 
                 CON(CH 3 ) 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 188 
                 CON(CH 3 ) 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 189 
                 CON(CH 3 ) 2   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 190 
                 CON(CH 3 ) 2   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 191 
                 CONHCH(CH 3 ) 2   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 192 
                 CONHCH(CH 3 ) 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 193 
                 CONHCH(CH 3 ) 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 194 
                 CONHCH(CH 3 ) 2   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 195 
                 CONHCH(CH 3 ) 2   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 196 
                 CONHC(CH 3 ) 3   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 197 
                 CONHC(CH 3 ) 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 198 
                 CONHC(CH 3 ) 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 199 
                 CONHC(CH 3 ) 3   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 200 
                 CONHC(CH 3 ) 3   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 201 
                 Cl 
                 H 
                 Br 
                 H 
                 Cl 
               
               
                 202 
                 Cl 
                 H 
                 SO 2 NH 2   
                 H 
                 Cl 
               
               
                 203 
                 Cl 
                 H 
                 SO 2 NH 2   
                 H 
                 Br 
               
               
                 204 
                 Br 
                 H 
                 SO 2 NH 2   
                 H 
                 Br 
               
               
                 205 
                 Cl 
                 CH 3   
                 CN 
                 Cl 
                 H 
               
               
                 206 
                 CH 3   
                 Cl 
                 NO 2   
                 H 
                 NO 2   
               
               
                 207 
                 NO 2   
                 CH 3   
                 Cl 
                 H 
                 NO 2   
               
               
                 208 
                 CN 
                 Cl 
                 CN 
                 Cl 
                 Cl 
               
               
                   
               
             
          
         
       
     
     Table 7: In formula II, R 1  is CH 3 , R 8  and R 10  are Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 7-1 to Table 7-208. 
     Table 8: In formula II, R 1  is H, R 8  and R 10  are F, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 8-1 to Table 8-208. 
     Table 9: In formula II, R 1  is H, R 8  is N(C 2 H 5 ) 2 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 9-1 to Table 9-208. 
     Table 10: In formula II, R 1  is H, R 8  is N(CH 3 ) 2 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 10-1 to Table 10-208. 
     Table 11: In formula II, R 1  is H, R 8  is NHCH 3 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 11-1 to Table 11-208. 
     Table 12: In formula II, R 1  is H, R 8  is OCH 3 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 12-1 to Table 12-208. 
     Table 13: In formula II, R 1  is H, R 8  is SCH 3 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 13-1 to Table 13-208. 
     Table 14: In formula II, R 1  is H, R 8  and R 10  are OCH 3 , R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 14-1 to Table 14-208. 
     Table 15: In formula II, R 1  is H, R 8  and R 10  are N(CH 3 ) 2 , R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 15-1 to Table 15-208. 
     Table 16: In formula II, R 1  is H, R 8  and R 10  are NHCH 3 , R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 16-1 to Table 16-208. 
     Table 17: In formula II, R 1  is H, R 8  and R 10  are SCH 3 , R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 17-1 to Table 17-208. 
     Table 18: In formula II, R 1  is H, R 8  is SO 2 CH 3 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 18-1 to Table 18-208. 
     Table 19: In formula II, R 1  is H, R 8  is OCH 2 CH═CH 2 , R 10  is Cl, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 19-1 to Table 19-208. 
     Table 20: In formula II, R 1  is H, R 8  is OCH 3 , R 10  is F, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 20-1 to Table 20-208. 
     Table 21: In formula II, R 1  is H, R 8  is N(CH 3 ) 2 , R 10  is F, R 2 -R 6  are listed in Table 6, the number of representative compounds are Table 21-1 to Table 21-208. 
     The present invention is also explained by the following compounds having general formula III with antitumor activity in Table 22-Table 30, but without being restricted thereby. 
     
       
                 
         
             
             
         
      
     
     Table 22: In general formula III, R 1  is H, R 8  is Cl, R 9  is NO 2 , R 2 , R 3 , R 4 , R 5  and R 6  (hereinafter abbreviated to R 2 -R 6 ) are listed in following Table, the numbers of representative compounds are Table 22-1 to Table 22-208. 
     
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 22 
               
               
                   
               
               
                 Number 
                 R 2   
                 R 3   
                 R 4   
                 R 5   
                 R 6   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 H 
                 H 
                 H 
                 H 
                 H 
               
               
                 2 
                 F 
                 H 
                 H 
                 H 
                 H 
               
               
                 3 
                 Cl 
                 H 
                 H 
                 H 
                 H 
               
               
                 4 
                 Br 
                 H 
                 H 
                 H 
                 H 
               
               
                 5 
                 I 
                 H 
                 H 
                 H 
                 H 
               
               
                 6 
                 CH 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 7 
                 OCH 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 8 
                 NO 2   
                 H 
                 H 
                 H 
                 H 
               
               
                 9 
                 CF 3   
                 H 
                 H 
                 H 
                 H 
               
               
                 10 
                 CN 
                 H 
                 H 
                 H 
                 H 
               
               
                 11 
                 CO 2 Ph 
                 H 
                 H 
                 H 
                 H 
               
               
                 12 
                 H 
                 F 
                 H 
                 H 
                 H 
               
               
                 13 
                 H 
                 Cl 
                 H 
                 H 
                 H 
               
               
                 14 
                 H 
                 Br 
                 H 
                 H 
                 H 
               
               
                 15 
                 H 
                 CF 3   
                 H 
                 H 
                 H 
               
               
                 16 
                 H 
                 H 
                 F 
                 H 
                 H 
               
               
                 17 
                 H 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 18 
                 H 
                 H 
                 Br 
                 H 
                 H 
               
               
                 19 
                 H 
                 H 
                 CH 3   
                 H 
                 H 
               
               
                 20 
                 H 
                 H 
                 OCH 3   
                 H 
                 H 
               
               
                 21 
                 H 
                 H 
                 OCF 3   
                 H 
                 H 
               
               
                 22 
                 H 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 23 
                 H 
                 H 
                 CN 
                 H 
                 H 
               
               
                 24 
                 H 
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 25 
                 H 
                 H 
                 CO 2 CH 3   
                 H 
                 H 
               
               
                 26 
                 H 
                 H 
                 SO 2 CH 3   
                 H 
                 H 
               
               
                 27 
                 H 
                 H 
                 CONHPh 
                 H 
                 H 
               
               
                 28 
                 H 
                 H 
                 CONHPh-4-CH 3   
                 H 
                 H 
               
               
                 29 
                 H 
                 H 
                 CONHPh-4-Cl 
                 H 
                 H 
               
               
                 30 
                 F 
                 F 
                 H 
                 H 
                 H 
               
               
                 31 
                 F 
                 H 
                 F 
                 H 
                 H 
               
               
                 32 
                 F 
                 H 
                 H 
                 F 
                 H 
               
               
                 33 
                 F 
                 H 
                 H 
                 H 
                 F 
               
               
                 34 
                 F 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 35 
                 F 
                 H 
                 H 
                 CF 3   
                 H 
               
               
                 36 
                 H 
                 F 
                 F 
                 H 
                 H 
               
               
                 37 
                 H 
                 F 
                 H 
                 F 
                 H 
               
               
                 38 
                 Cl 
                 Cl 
                 H 
                 H 
                 H 
               
               
                 39 
                 Cl 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 40 
                 Cl 
                 H 
                 H 
                 Cl 
                 H 
               
               
                 41 
                 Cl 
                 H 
                 H 
                 H 
                 Cl 
               
               
                 42 
                 Cl 
                 H 
                 H 
                 H 
                 CH 3   
               
               
                 43 
                 H 
                 Cl 
                 Cl 
                 H 
                 H 
               
               
                 44 
                 H 
                 Cl 
                 H 
                 Cl 
                 H 
               
               
                 45 
                 Cl 
                 H 
                 Br 
                 H 
                 H 
               
               
                 46 
                 Br 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 47 
                 Cl 
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 48 
                 Cl 
                 CH 3   
                 H 
                 H 
                 H 
               
               
                 49 
                 Cl 
                 H 
                 H 
                 CF 3   
                 H 
               
               
                 50 
                 Cl 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 51 
                 Cl 
                 H 
                 H 
                 NO 2   
                 H 
               
               
                 52 
                 Cl 
                 H 
                 H 
                 CN 
                 H 
               
               
                 53 
                 Cl 
                 H 
                 H 
                 CH 3   
                 H 
               
               
                 54 
                 NO 2   
                 H 
                 H 
                 Cl 
                 H 
               
               
                 55 
                 CN 
                 H 
                 H 
                 Cl 
                 H 
               
               
                 56 
                 CH 3   
                 H 
                 H 
                 Cl 
                 H 
               
               
                 57 
                 CH 3   
                 H 
                 H 
                 H 
                 Cl 
               
               
                 58 
                 CH 3   
                 Cl 
                 H 
                 H 
                 H 
               
               
                 59 
                 CF 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 60 
                 F 
                 H 
                 CN 
                 H 
                 H 
               
               
                 61 
                 Cl 
                 H 
                 CN 
                 H 
                 H 
               
               
                 62 
                 Br 
                 H 
                 CN 
                 H 
                 H 
               
               
                 63 
                 NO 2   
                 H 
                 CN 
                 H 
                 H 
               
               
                 64 
                 t-C 4 H 9   
                 H 
                 CN 
                 H 
                 H 
               
               
                 65 
                 OCH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 66 
                 CO 2 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 67 
                 SO 2 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 68 
                 H 
                 F 
                 CN 
                 H 
                 H 
               
               
                 69 
                 H 
                 Cl 
                 CN 
                 H 
                 H 
               
               
                 70 
                 H 
                 Br 
                 CN 
                 H 
                 H 
               
               
                 71 
                 H 
                 NO 2   
                 CN 
                 H 
                 H 
               
               
                 72 
                 H 
                 CH 3   
                 CN 
                 H 
                 H 
               
               
                 73 
                 H 
                 OCH 3   
                 CN 
                 H 
                 H 
               
               
                 74 
                 CN 
                 H 
                 Cl 
                 H 
                 H 
               
               
                 75 
                 CF 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 76 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 77 
                 H 
                 CN 
                 Cl 
                 H 
                 H 
               
               
                 78 
                 H 
                 CH 3   
                 Cl 
                 H 
                 H 
               
               
                 79 
                 H 
                 CF 3   
                 Cl 
                 H 
                 H 
               
               
                 80 
                 CH 3   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 81 
                 CH 3   
                 H 
                 CH 3   
                 H 
                 H 
               
               
                 82 
                 CH 3   
                 H 
                 H 
                 CH 3   
                 H 
               
               
                 83 
                 CH 3   
                 H 
                 CN 
                 H 
                 H 
               
               
                 84 
                 CH 3   
                 H 
                 CF 3   
                 H 
                 H 
               
               
                 85 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 H 
               
               
                 86 
                 H 
                 CF 3   
                 CN 
                 H 
                 H 
               
               
                 87 
                 H 
                 CH 3   
                 CN 
                 H 
                 H 
               
               
                 88 
                 NO 2   
                 H 
                 Cl 
                 H 
                 H 
               
               
                 89 
                 NO 2   
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 90 
                 CN 
                 H 
                 NO 2   
                 H 
                 H 
               
               
                 91 
                 F 
                 F 
                 F 
                 H 
                 H 
               
               
                 92 
                 F 
                 H 
                 F 
                 H 
                 F 
               
               
                 93 
                 F 
                 H 
                 Cl 
                 H 
                 F 
               
               
                 94 
                 F 
                 H 
                 F 
                 H 
                 NO 2   
               
               
                 95 
                 F 
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 96 
                 Cl 
                 Cl 
                 Cl 
                 H 
                 H 
               
               
                 97 
                 Cl 
                 H 
                 Cl 
                 Cl 
                 H 
               
               
                 98 
                 Cl 
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 99 
                 Cl 
                 Cl 
                 H 
                 Cl 
                 H 
               
               
                 100 
                 Cl 
                 H 
                 Br 
                 H 
                 Cl 
               
               
                 101 
                 Cl 
                 H 
                 CF 3   
                 H 
                 Cl 
               
               
                 102 
                 Cl 
                 H 
                 OCF 3   
                 H 
                 Cl 
               
               
                 103 
                 Cl 
                 H 
                 CH 3   
                 H 
                 Cl 
               
               
                 104 
                 Cl 
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 105 
                 Cl 
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 106 
                 Cl 
                 H 
                 NO 2   
                 Cl 
                 H 
               
               
                 107 
                 Cl 
                 H 
                 CO 2 CH 3   
                 H 
                 Cl 
               
               
                 108 
                 Cl 
                 H 
                 SO 2 CH 3   
                 H 
                 Cl 
               
               
                 109 
                 Cl 
                 H 
                 SO 2 NH 2   
                 H 
                 Cl 
               
               
                 110 
                 Cl 
                 H 
                 SO 2 NH 2   
                 H 
                 Br 
               
               
                 111 
                 Br 
                 H 
                 SO 2 NH 2   
                 H 
                 Br 
               
               
                 112 
                 Cl 
                 H 
                 t-C 4 H 9   
                 H 
                 Cl 
               
               
                 113 
                 Cl 
                 H 
                 CONHPh 
                 H 
                 Cl 
               
               
                 114 
                 Cl 
                 H 
                 CONHPh-4-Cl 
                 H 
                 Cl 
               
               
                 115 
                 Cl 
                 H 
                 CO 2 Na 
                 H 
                 Cl 
               
               
                 116 
                 Cl 
                 H 
                 COOH 
                 H 
                 Cl 
               
               
                 117 
                 Cl 
                 H 
                 NO 2   
                 H 
                 CH 3   
               
               
                 118 
                 Cl 
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 119 
                 Cl 
                 CH 3   
                 Cl 
                 H 
                 H 
               
               
                 120 
                 Cl 
                 H 
                 Cl 
                 H 
                 CN 
               
               
                 121 
                 Cl 
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 122 
                 Cl 
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 123 
                 Cl 
                 H 
                 NO 2   
                 H 
                 Br 
               
               
                 124 
                 Cl 
                 H 
                 OCF 2 CHFCF 3   
                 Cl 
                 H 
               
               
                   
               
               
                 125 
                 H 
                 Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 Cl 
                 H 
               
               
                   
               
               
                 126 
                 Br 
                 H 
                 OCF 3   
                 H 
                 Br 
               
               
                 127 
                 Br 
                 H 
                 Br 
                 H 
                 Br 
               
               
                 128 
                 Br 
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 129 
                 Br 
                 H 
                 NO 2   
                 H 
                 Br 
               
               
                 130 
                 Br 
                 H 
                 NO 2   
                 H 
                 CN 
               
               
                 131 
                 CH 3   
                 H 
                 CH 3   
                 H 
                 CH 3   
               
               
                 132 
                 CH 3   
                 H 
                 t-C 4 H 9   
                 H 
                 CH 3   
               
               
                 133 
                 C 2 H 5   
                 H 
                 Cl 
                 H 
                 C 2 H 5   
               
               
                 134 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 Br 
               
               
                 135 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 NO 2   
               
               
                 136 
                 CH 2   
                 H 
                 CO 2 CH 3   
                 H 
                 CN 
               
               
                 137 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 OCH 3   
               
               
                 138 
                 CH 3   
                 H 
                 CO 2 CH 3   
                 H 
                 CF 3   
               
               
                 139 
                 CH 3   
                 Cl 
                 NO 2   
                 H 
                 H 
               
               
                 140 
                 CH 3   
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 141 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 F 
               
               
                 142 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 Cl 
               
               
                 143 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 Br 
               
               
                 144 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 145 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CN 
               
               
                 146 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 OCH 3   
               
               
                 147 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CF 3   
               
               
                 148 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 CO 2 CH 3   
               
               
                 149 
                 C 2 H 5   
                 H 
                 NO 2   
                 H 
                 SO 2 CH 3   
               
               
                 150 
                 Cl 
                 H 
                 CF 3   
                 H 
                 F 
               
               
                 151 
                 Cl 
                 H 
                 CF 3   
                 H 
                 Br 
               
               
                 152 
                 Cl 
                 H 
                 CF 3   
                 H 
                 NO 2   
               
               
                 153 
                 Cl 
                 H 
                 CN 
                 H 
                 NO 2   
               
               
                 154 
                 Cl 
                 H 
                 CF 3   
                 H 
                 OCH 3   
               
               
                 155 
                 Cl 
                 H 
                 CF 3   
                 H 
                 CO 2 CH 3   
               
               
                 156 
                 F 
                 H 
                 CF 3   
                 H 
                 Br 
               
               
                 157 
                 F 
                 H 
                 CF 3   
                 H 
                 NO 2   
               
               
                 158 
                 F 
                 H 
                 CF 3   
                 H 
                 OCH 3   
               
               
                 159 
                 F 
                 H 
                 CF 3   
                 H 
                 CO 2 CH 3   
               
               
                 160 
                 Cl 
                 H 
                 SO 2 NHCH 3   
                 H 
                 Cl 
               
               
                 161 
                 Cl 
                 H 
                 SO 2 N(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 162 
                 Cl 
                 H 
                 CO 2 NH 4   
                 H 
                 Cl 
               
               
                 163 
                 Cl 
                 H 
                 CONH 2   
                 H 
                 Cl 
               
               
                 164 
                 Cl 
                 H 
                 CONHCH 3   
                 H 
                 Cl 
               
               
                 165 
                 Cl 
                 H 
                 CON(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 166 
                 Cl 
                 H 
                 CONHCH(CH 3 ) 2   
                 H 
                 Cl 
               
               
                 167 
                 Cl 
                 H 
                 CONHC(CH 3 ) 3   
                 H 
                 Cl 
               
               
                 168 
                 CH 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 169 
                 NO 2   
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 170 
                 NO 2   
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 171 
                 NO 2   
                 H 
                 CF 3   
                 H 
                 NO 2   
               
               
                 172 
                 NO 2   
                 H 
                 CN 
                 CF 3   
                 H 
               
               
                 173 
                 CN 
                 H 
                 Cl 
                 H 
                 NO 2   
               
               
                 174 
                 CN 
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 175 
                 CN 
                 H 
                 Cl 
                 H 
                 CN 
               
               
                 176 
                 CN 
                 H 
                 Cl 
                 H 
                 CF 3   
               
               
                 177 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 178 
                 CH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 179 
                 NO 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 180 
                 NO 2   
                 H 
                 Cl 
                 Cl 
                 H 
               
               
                 181 
                 CF 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 182 
                 OCH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 183 
                 NO 2   
                 H 
                 Cl 
                 H 
                 F 
               
               
                 184 
                 NO 2   
                 H 
                 Cl 
                 H 
                 Br 
               
               
                 185 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CF 3   
               
               
                 186 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CO 2 CH 3   
               
               
                 187 
                 NO 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 188 
                 CN 
                 H 
                 NO 2   
                 H 
                 NO 2   
               
               
                 189 
                 COOH 
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 190 
                 COOH 
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 191 
                 COOH 
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 192 
                 COOH 
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 193 
                 COOH 
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 194 
                 CO 2 CH 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 195 
                 CO 2 CH 3   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 196 
                 CONHCH 3   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 197 
                 CONHCH 3   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 198 
                 CONHCH 3   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 199 
                 CONHCH 3   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 200 
                 CONHCH 3   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 201 
                 CONH 2   
                 H 
                 CN 
                 H 
                 CH 3   
               
               
                 202 
                 CONH 2   
                 H 
                 Cl 
                 H 
                 Cl 
               
               
                 203 
                 CONH 2   
                 H 
                 Cl 
                 H 
                 CH 3   
               
               
                 204 
                 CONH 2   
                 H 
                 Br 
                 H 
                 CH 3   
               
               
                 205 
                 CONH 2   
                 H 
                 CN 
                 H 
                 Cl 
               
               
                 206 
                 NO 2   
                 Cl 
                 CF 3   
                 H 
                 NO 2   
               
               
                 207 
                 Cl 
                 H 
                 NO 2   
                 Cl 
                 NO 2   
               
               
                 208 
                 Cl 
                 H 
                 Cl 
                 Cl 
                 NO 2   
               
               
                   
               
             
          
         
       
     
     Table 23: In formula III, R 1  and R 9  are H, R 8  is Cl, R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 23-1 to Table 23-208. 
     Table 24: In formula III, R 1  is CH 3 , R 8  is Cl, R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 24-1 to Table 24-208. 
     Table 25: In formula III, R 1  is H, R 8  is OCH 3 , R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 25-1 to Table 25-208. 
     Table 26: In formula III, R 1  is H, R 8  is SCH 3 , R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 26-1 to Table 26-208. 
     Table 27: In formula III, R 1  is H, R 8  is NHCH 3 , R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 27-1 to Table 27-208. 
     Table 28: In formula III, R 1  is H, R 8  is N(CH 3 ) 2 , R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 28-1 to Table 28-208. 
     Table 29: In formula III, R 1  is H, R 8  is OCH 2 CF 3 , R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 29-1 to Table 29-208. 
     Table 30: In formula III, R 1  and R 8  is H, R 9  is NO 2 , R 2 -R 6  are listed in Table 22, the number of representative compounds are Table 30-1 to Table 30-208. 
     The compounds having formula I in present invention have been reported in prior art, which are commercial available or can be prepared according to the following method. The reaction is as follow, wherein the definitions of substituents are as defined above: 
     
       
                 
         
             
             
         
      
     
     Wherein: X and Y are different, respectively selected from halogen atom or amino; Z is halogen atom; R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10  and R 11  are defined respectively as mentioned above; R 1  are defined as mentioned above, but R 1 ≠H. 
     According to the above preparation method, treatment of intermediate IV with intermediate V at the presence of base gives compounds I-a of general formula I (R 1 ═H), which react with Z—R 1  to give compounds I-b of general formula I (R 1 ≠H). 
     The proper base mentioned above may be selected from potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide and so on. 
     The reaction can be carried out in proper solvent, and the proper solvent mentioned may be selected from tetrahydrofuran, acetonitrile, toluene, xylene, benzene, DMF, N-methylpyrrolidone, DMSO, acetone or butanone and so on. 
     The proper reaction temperature is from room temperature to boiling point of solvent, generally is 20-100° C. 
     The reaction time is in the range of 30 minutes to 20 hours, generally is 1-10 hours. 
     Intermediates IV are commercially available, or prepared according to the known methods, such as referring to Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 45B(4), 972-975, 2006; Tetrahedron Letters, 44(21), 4085-4088, 2003; PL174903, etc. 
     Intermediate V can be prepared according to the known methods, such as referring to JP2003292476, 052010160695, etc. 
     The nitration of compounds of general formula I, in which at least one of R 2 , R 4 , R 6 , R 9  or R 11  is H, can add one or several NO 2  groups to these compounds of general formula I. 
     The halogenation of substituted diphenylamine compounds of general formula I, in which R 2 , R 4 , R 6 , R 7 , R 9  or R 11  is not halogen atom, can add one or several halogen atoms to these compounds of general formula I. 
     The compounds of general formula I, in which R 8  and R 10  are alkylamino, alkoxy or alkylthio, can be prepared from the reaction of compounds of general formula I whose R 8  and R 10  are halogen atom with amine, alcohol or mercaptan (or their salts), or referring to the preparation method in  Journal of Medicinal Chemistry,  1978, 21(9), 906-913. 
     The compounds of general formula I, in which R 8  and R 10  are alkylsulfonyl and alkylcarbonyloxy, can be prepared according to the preparation method in  Journal of Medicinal Chemistry,  1978, 21(9), 906-913. 
     The salts of compounds having general formula I can be prepared from the reaction of the compounds of general formula I with corresponding acid according to routine method. The proper acid may be selected from hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid; The preferred acid are selected from hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, methylsulfonic acid or p-toluenesulfonic acid. 
     The present invention includes the formulations, which were made from the compounds having the general formula I as active ingredient, and preparation thereof. The preparation of formulations: Dissolve the compounds of present invention in water soluble organic solvents, the ionicity of surfactant, water soluble lipid, all kinds of cyclodextrin, fatty acid, fatty acid ester, phospholipids or their combination solvents, and add physiological saline or 1-20% of carbohydrates. Mentioned organic solvents include polyethylene glycol (PEG), ethanol, propylene glycol or their combination solvents. 
     The compounds having the general formula I in present invention and their salt and prodrug can be used to prepare the drugs or formulations to cure, prevent or alleviate cancer. The active ingredients are composed of one or more than two diphenylamine compounds having the general formula I. Especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer. 
     The compounds in present invention can be used as active ingredients of antitumor drug, which can be used alone or combined with other antitumorantiviral drugs. The drug combination process in present invention, using at least one of the compounds and its active derivatives with other one or more antitumorantiviral drugs, are used together to increase the overall effect. The dose and drug administration time of combination therapy are based on the most reasonable treatment effect in the different situations. 
     The formulations include the effective dose of the compounds having general formula I. The “effective dose” refers to the compound dosage, which are effective to cure cancer. The effective dose or dose can be different based on the suggestions of experienced person at different conditions. For instance, the different usage of drug based on different cancers; the dose of drug also can be changed based on whether it shares with other therapeutic method, such as antitumor or antiviral drugs. The drug can be prepared for any useable formulations. The salts of compounds also can be used if the alkaline or acidic compounds can formed the non-toxic acids or salts. The organic acids/salts in pharmacy include anion salts, which are formed with acids, such as p-toluenesulfonic acid, methylsulfonic acid, acetic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or glycerophosphoric acid; the inorganic salts include chloride, bromide, fluoride, iodide, sulfate, nitrate, bicarbonate, carbonate or phosphate. For example, the alkaline compounds, such as amines can form salts with suitable acids; acids can form salts with alkalis or alkaline earth. 
     The compounds in present invention having general formula I general easily dissolves in organic solvent, water soluble solvent and their mixture with water. The water soluble solvents prefer alcohol, polyethylene glycol, N-methyl-2-pyrrolidone, N,N-dimethyl acetamide, N,N-dimethyl formamide, dimethylsulfoxide, acetonitrile and their mixture. Mentioned alcohols prefer methanol, ethanol, isopropanol, glycerol or ethylene glycol. The compounds in present invention mix with common drug carrier to form formulations. Dissolve the compounds of present invention in water soluble organic solvents, aprotic solvent, water soluble lipid, cyclodextrin, fatty acid, phospholipids or their combination solvents, and add physiological saline or 1-20% of carbohydrates, such as glucose aqueous solution. The stability formulations made by this way are used for animal and clinical. 
     The drugs were made from the active ingredients of general formula I compounds, which can dose by oral medication or parenteral route, also by implantable medication pump and other methods. Where the parenteral route refer to injection or drip technology through subcutaneous intradermal, intramuscular, intravenous, arteries, atrium, synovium, sternum, intrathecal, wound area, encephalic, etc. The formulations were mixed using conventional method by technicist, which are used for animal and clinical, including tablets, pills, capsule, granule, syrup, injection, freeze-dried powder injection, emulsion, powder, freeze-dried powder, drop pill, milk suspension, aqueous suspension, colloid, colloidal solution, sustained-release suspensions, nanoparticle or other formulations. 
     The compounds having the general formula I in present invention can be used to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The cancers include but not limited to colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention is illustrated by the following examples, but without being restricted thereby. (All raw materials are commercially available unless otherwise specified.) 
     PREPARATION EXAMPLES 
     Example 1 
     Preparation of Compound Table 6-1 
     
       
                 
         
             
             
         
      
     
     0.35 g (3.76 mmol) of aniline and 0.30 g (7.52 mmol) of sodium hydroxide were added into 40 mL of DMF, and 1.00 g (3.76 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and filtered to give white solid. The solid was washed twice by 30 ml water and twice by 20 ml petroleum ether, 0.65 g of compound Table 6-1 as white solid was obtained, m.p. 226-228° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 7.22 (d, 2H, Ph-2,6-2H, J=7.5 Hz), 7.40-7.46 (m, 3H, Ph-3,4,5-3H). 
     Example 2 
     Preparation of Compound Table 6-33 
     
       
                 
         
             
             
         
      
     
     1.03 g (8 mmol) of 2,6-difluoroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 1.65 g of compound table 6-33 as yellow solid, m.p. 264-266° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.70 (s, 1H, NH), 7.07 (t, 2H, Ph-3,5-2H, J=8.1 Hz), 7.37 (m, 1H, Ph-4-1H). 
     Example 3 
     Preparation of Compound Table 6-39 
     
       
                 
         
             
             
         
      
     
     The preparation is same to compound Table 6-1, brown black solid, m.p. 209-212° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.95 (s, 1H, NH), 7.20 (d, 1H, Ph-6-H, J=8.1 Hz), 7.36 (dd, 1H, Ph-5-H,  3 J=8.7 Hz,  4 J=2.7 Hz), 7.54 (d, 1H, Ph-3-H, J=2.4 Hz). 
     Example 4 
     Preparation of Compound Table 6-91 
     
       
                 
         
             
             
         
      
     
     0.68 g (2 mmol) of compound table 6-33 was dissolved in 20 mL of concentrated sulfuric acid and cooled by ice-bath, the mixed acid (4 mmol of nitric acid and 6 mmol of sulfuric acid) was added dropwise to the reaction solution under stirring to keep the temperature below 20° C. Then the reaction mixture was stirred for another 5 min. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into ice water, extracted with ethyl acetate, the extract was washed by saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 0.40 g of compound table 6-91 as white solid, m.p. 204-206° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.70 (s, 1H, NH), 7.97-8.01 (dd, 2H, Ph-3,5-2H,  3 J=10.8 Hz,  4 J=3.0 Hz). 
     Example 5 
     Preparation of Compound Table 6-93 
     
       
                 
         
             
             
         
      
     
     1.57 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 1.91 g of compound table 6-39 as light yellow solid, m.p. 182-184° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H). 
     Example 6 
     Preparation of Compound Table 6-99 
     
       
                 
         
             
             
         
      
     
     0.35 g (1.3 mmol) of 2,6-dichloro-4-nitroaniline and 0.10 g (2.6 mmol) of sodium hydroxide were added into 40 mL of DMF, and 0.27 g (1.3 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 0.48 g of compound table 6-99 as yellow solid, m.p. 250-252° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.93 (s, 1H, NH), 8.34 (s, 2H, Ph-3,5-2H). 
     Example 7 
     Preparation of Compound Table 6-100 
     
       
                 
         
             
             
         
      
     
     10.33 g (39 mmol) of methyl 4-amino-3,5-dichlorobenzoate (preparation refer to WO2010060379, CN101337940) and 3.12 g (78 mmol) of sodium hydroxide were added into 60 mL of DMF, and 10.37 g (39 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/5, as an eluent) to give 13.65 g of compound table 6-100 as yellow solid, m.p. 229-231° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 3.96 (s, 3H, CH 3 ), 6.92 (s, 1H, NH), 8.11 (s, 2H, Ph-2,6-2H). 
     Example 8 
     Preparation of Compound Table 6-104 
     
       
                 
         
             
             
         
      
     
     (1) Preparation of Compound Table 6-106 
     13.31 g (31 mmol) of compound Table 6-100 was dissolved in mixed solution of THF and water (volume ratio=1/1), and 2.45 g (61 mmol) of sodium hydroxide was added to the reaction solution followed by heating for 5 h at 50° C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the aqueous phase was acidized by diluted hydrochloric acid, and filtered to give compound Table 6-106 as yellow solid, dried for the next step. 
     (2) Preparation of Compound Table 6-106a 
     5.54 g (12.72 mmol) of compound Table 6-106 was added to 100 ml of petroleum ether, and two drops of DMF and 2.27 g (19.08 mmol) of thionyl chloride were added to the reaction solution followed by refluxing for 2 h at 85° C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to obtain compound Table 6-106a. 
     (3) Preparation of Compound Table 6-104 
     0.12 g (0.91 mmol) of p-chloroaniline and 0.23 g (2.27 mmol) of triethylamine were dissolved in anhydrous THF, then 0.40 g (0.91 mmol) of compound Table 6-106a was added dropwise to the reaction solution followed by heating for 5 h at 45° C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/3, as an eluent) to give 0.23 g of compound table 6-104 as white solid, m.p. 275-276° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 7.31-7.35 (m, 2H, 4-Cl-Ph-2,6-2H), 7.81 (d, 2H, 4-Cl-Ph-3,5-2H, J=9.0 Hz), 8.13 (dd, 2H, Ph-2,6-2H,  3 J=15.7 Hz,  4 J=1.2 Hz), 10.50 (d, 1H, CONH, J=12.9 Hz). 
     Example 9 
     Preparation of Compound Table 6-112 
     
       
                 
         
             
             
         
      
     
     2.63 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 3.22 g of compound table 6-112 as brown solid, m.p. 238-239° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H). 
     Example 10 
     Preparation of Compound Table 14-99 
     
       
                 
         
             
             
         
      
     
     0.55 g (1.3 mmol) of compound Table 6-99 and 0.14 g (2.5 mmol) of sodium methoxide were dissolved in 20 ml of DMSO, followed by heating for 8 h at 95° C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/4, as an eluent) to give 0.16 g of compound table 14-99 as yellow solid, m.p. 151-153° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 4.23 (t, 6H, OCH 3 , J=6.6 Hz), 6.78 (br, 1H, NH), 8.31 (d, 2H, Ph-3,5-2H, J=3.9 Hz). 
     Example 11 
     Preparation of Compound Table 22-39 
     
       
                 
         
             
             
         
      
     
     0.81 g (0.005 mol) of 2,4-dichloroaniline was added in portions to a suspension of 0.4 g (0.01 mol) of NaH (60%) and 20 mL of THF, the mixture was stirred for 30 min after addition, 1.56 g (0.006 mol) of 2,6-dichloro-3,5-dinitrotulune in 30 mL of THF was added within 30 min, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure, then the residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/20, as an eluent) to give 1.37 g of compound table 22-39 as yellow solid, m.p. 136-137° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.14 (s, 3H), 6.53 (d, 1H), 7.17 (d, 1H), 7.49 (s, 1H), 8.68 (s, 1H), 8.93 (s, 1H). 
     Example 12 
     Preparation of Compound Table 22-101 
     
       
                 
         
             
             
         
      
     
     The preparation is same to compound Table 22-39, m.p. 143-144° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 1.98 (s, 3H), 7.66 (s, 2H), 8.70 (s, 1H), 9.10 (s, 1H). 
     Example 13 
     Preparation of Compound Table 22-105 
     
       
                 
         
             
             
         
      
     
     0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portions to a suspension of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 30 min after addition, 1.20 g (0.0048 mol) of 2,6-dichloro-3,5-dinitrotulune was added in portions within 30 min, then stirred for another 3 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/10, as an eluent) to give 1.20 g of compound table 22-105 as yellow solid, m.p. 157-158° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.02 (s, 3H), 8.29 (s, 2H), 8.65 (s, 1H), 8.95 (s, 1H). 
     Example 14 
     Preparation of Compound Table 22-120 
     
       
                 
         
             
             
         
      
     
     The preparation is same to compound Table 22-39, m.p. 148-150° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.07 (s, 3H), 7.53 (s, 1H), 7.72 (s, 1H), 8.71 (s, 1H), 8.97 (s, 1H). 
     Example 15 
     Preparation of Compound Table 22-121 
     
       
                 
         
             
             
         
      
     
     0.56 g (0.0015 mol) of compound table 22-39 was dissolved in 5 mL of concentrated sulfuric acid (96%, the same below) and cooled to 0° C., 0.15 g of fuming nitric acid (95%) and 3 mL of concentrated sulfuric acid was mixed evenly and added to the flask, then the reaction mixture was stirred for another 5 min. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into ice water, the solid precipitated was filtered, and the filter mass was washed with water and dried to give 0.59 g of compound table 22-121 as brown solid, m.p. 156-158° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.09 (s, 3H), 7.66 (s, 1H), 8.01 (s, 1H), 8.60 (s, 1H), 9.75 (s, 1H). 
     Example 16 
     Preparation of Compound Table 22-153 
     
       
                 
         
             
             
         
      
     
     The preparation is same to compound Table 22-39, m.p. 204-206° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.23 (s, 3H), 7.87 (s, 1H), 8.38 (s, 1H), 8.51 (s, 1H), 10.00 (s, 1H). 
     Example 17 
     Preparation of Compound Table 22-206 
     
       
                 
         
             
             
         
      
     
     The intermediate M prepared by the procedure of Example 13 was nitrated according to Example 2 to give compound Table 22-206 as reddish-brown solid, m.p. 136-138° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.41 (s, 3H), 8.50 (s, 1H), 8.72 (s, 1H), 10.10 (s, 1H). 
     Example 18 
     Preparation of Compound Table 24-39 
     
       
                 
         
             
             
         
      
     
     0.38 g (0.001 mol) of compound table 22-39 was added to a suspension of 0.10 g (0.0025 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 1 h and then added thereto 0.43 g (0.003 mol) of CH 3 I, the resulting mixture was allowed to react for 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/10, as an eluent) to give 0.15 g of compound table 22-39 as yellow solid, m.p. 142-144° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 2.54 (s, 3H), 3.31 (s, 3H), 7.09 (d, 1H), 7.25 (d, 2H), 8.04 (s, 1H). 
     Example 19 
     Preparation of Compound Table 27-105 
     
       
                 
         
             
             
         
      
     
     0.42 g of compound table 22-105 (0.001 mol) was added to a microwave vial and dissolved with 2.5 mL of DMSO, 1 mL of methylamine aqueous solution (25%) was added, the vial was lidded and put into the microwave reactor, then the reaction was carried out at 150° C. for 40 min. The reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=120, as an eluent) to give 0.25 g of compound table 27-105 as yellow solid, m.p. 218-219° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 1.70 (s, 3H), 3.09 (d, 3H), 8.25 (d, 1H), 8.31 (s, 2H), 9.12 (s, 1H), 9.58 (s, 1H). 
     Example 20 
     Preparation of Compound Table 29-105 
     
       
                 
         
             
             
         
      
     
     0.42 g (1 mmol) of compound Table 22-105 and 2 mmol of sodium 2,2,2-trifluoroethanolate (made from trifluoroethanol and sodium) were dissolved in 3 ml of DMSO, heating to 150° C. for 10 min in microwave synthesizer (Biotage). Then the reaction mixture was poured into saturated brine, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=120, as an eluent) to give 0.21 g of compound table 29-105 as yellow solid, m.p. 126-128° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 1.83 (s, 3H), 4.42 (q, 2H), 8.30 (s, 2H), 8.85 (s, 1H), 9.20 (s, 1H). 
     Example 21 
     Preparation of Compound Table 30-105 
     
       
                 
         
             
             
         
      
     
     0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portions to a suspension of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 30 min after addition, 1.04 g (0.0048 mol) of 2-chloro-1-methyl-3,5-dinitrobenzene was added in portions within 30 min, then stirred for another 3 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90° C.)=1/10, as an eluent) to give 0.96 g of compound Table 30-105 as yellow solid, m.p. 146-148° C. 
       1 H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC 3 ) δ(ppm): 1.96 (s, 3H), 8.26 (d, 1H), 8.29 (s, 2H), 8.95 (d, 1H), 9.00 (s, 1H). 
     Other compounds of the present invention were prepared according to the above examples. 
     Physical properties and  1 HNMR spectrum ( 1 HNMR, 300 MHz, internal standard: TMS, ppm) of some compounds of this invention are as follows: 
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
               
               
                 Table 
                 Compound 
                 Mp. (° C.) and  1 HNMR (300 MHz, internal standard: TMS, solvent 
               
               
                 No. 
                 No. 
                 CDCl 3 ) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 6 
                 3 
                 m.p. 208-210° C. δ (CDCl 3 ): 7.03 (s, 1H, NH), 7.27-7.38 (m, 3H, 
               
               
                   
                   
                 Ph-3,5,6-3H), 7.49-7.55 (m, 1H, Ph-4-H). 
               
               
                 6 
                 6 
                 m.p. 212-214° C. δ (CDCl 3 ): 2.29 (s, 3H, CH 3 ), 7.00 (s, 1H, NH), 
               
               
                   
                   
                 7.15 (d, H, Ph-6-H, J = 7.5 Hz), 7.28-7.34 (m, 3H, Ph-3,4,5-3H). 
               
               
                 6 
                 10 
                 m.p. 258-260° C. δ (CDCl 3 ): 7.12 (s, 1H, NH), 7.24 (d, 1H, 
               
               
                   
                   
                 Ph-6-H, J = 7.5 Hz), 7.47 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.68 (t, 1H, 
               
               
                   
                   
                 Ph-5-H, J = 7.5 Hz), 7.78 (d, 1H, Ph-3-H, J = 7.8 Hz). 
               
               
                 6 
                 14 
                 m.p. 236-238° C. δ (CDCl 3 ): 7.12 (s, 1H, NH), 7.28-7.40 (m, 1H, 
               
               
                   
                   
                 Ph-6-H), 7.41-7.52 (m, 2H, Ph-2,4-2H), 7.54-7.62 (m, 1H, 
               
               
                   
                   
                 Ph-5-H). 
               
               
                 6 
                 19 
                 m.p. 144-146° C. δ (CDCl 3 ): 1.30 (s, 9H, t-C 4 H 9 ), 6.65 (m, 2H, 
               
               
                   
                   
                 Ph-2,6-2H), 7.16 (s, 1H, NH), 7.18 (m, 2H, Ph-3,5-2H). 
               
               
                 6 
                 21 
                 m.p. 204-206° C. δ (CDCl 3 ): 7.09 (s, 1H, NH), 7.22-7.32 (m, 4H, 
               
               
                   
                   
                 Ph-2,3,5,6-4H). 
               
               
                 6 
                 23 
                 m.p. 259-261° C. δ (CDCl 3 ): 7.00 (s, 1H, NH), 7.17 (d, 2H, 
               
               
                   
                   
                 Ph-2,6-2H, J = 8.7 Hz), 7.42 (d, 2H, Ph-3,5-2H, J = 9.0 Hz). 
               
               
                 6 
                 25 
                 m.p. 246-248° C. δ (CDCl 3 ): 2.29 (s, 3H, COOCH 3 ), 7.08 (s, 1H, 
               
               
                   
                   
                 NH), 7.17 (d, 2H, Ph-3,5-2H, J = 8.7 Hz), 8.10 (d, 2H, Ph-2,6-2H, 
               
               
                   
                   
                 J = 8.7 Hz). 
               
               
                 6 
                 31 
                 m.p. 206-208° C. δ (CDCl 3 ): 6.88 (s, 1H, NH), 6.99 (t, 2H, 
               
               
                   
                   
                 Ph-5,6-2H, J = 8.1 Hz), 7.32 (d, 1H, Ph-3-H, J = 2.4 Hz). 
               
               
                 6 
                 35 
                 m.p. 209-212° C. 6.93 (s, 1H, NH), 7.34 (t, 1H, Ph-3-H, 
               
               
                   
                   
                 J = 9.0 Hz), 7.52 (d, 1H, Ph-4-H, J = 7.2 Hz), 7.58-7.65 (m, 1H, 
               
               
                   
                   
                 Ph-3-H). 
               
               
                 6 
                 38 
                 m.p. 218-220° C. δ (CDCl 3 ): 7.03 (s, 1H, NH), 7.13 (dd, 1H, 
               
               
                   
                   
                 Ph-6-H,  3 J = 8.1 Hz,  4 J = 0.9 Hz), 7.28 (t, 1H, Ph-5-H, J = 8.1 Hz), 
               
               
                   
                   
                 7.47 (dd, 1H, Ph-4-H,  3 J = 8.1 Hz,  4 J = 0.9 Hz). 
               
               
                 6 
                 41 
                 m.p. 235-237° C. δ (CDCl 3 ): 6.61 (s, 1H, NH), 7.36 (t, 1H, 
               
               
                   
                   
                 Ph-4-H, J = 7.2 Hz), 7.45 (d, 2H, Ph-3,5-2H, J = 7.2 Hz). 
               
               
                 6 
                 42 
                 m.p. 240-242° C. δ (CDCl 3 ): 2.32 (s, 3H, Ph—CH 3 ), 6.93 (s, 1H, 
               
               
                   
                   
                 NH), 7.22-7.35 (m, 3H, Ph-3,4,5-H). 
               
               
                 6 
                 44 
                 m.p. 238-242° C. δ (CDCl 3 ): 6.95 (s, 1H, NH), 7.05 (d, 2H, 
               
               
                   
                   
                 Ph-2,6-2H, J = 1.8 Hz), 7.32 (d, 1H, Ph-4-H, J = 1.5 Hz). 
               
               
                 6 
                 47 
                 m.p. 166-168° C. δ (CDCl 3 ): 7.00 (s, 1H, NH), 7.20 (d, 1H, 
               
               
                   
                   
                 Ph-6-H, J = 8.4 Hz), 7.57 (dd, 1H, Ph-5-H,  3 J = 8.4 Hz,  4 J = 1.5 Hz), 
               
               
                   
                   
                 7.78 (s, 1H, Ph-3-H). 
               
               
                 6 
                 48 
                 m.p. 197-199° C. δ (CDCl 3 ): 7.02 (s, 1H, NH), 7.45 (s, 1H, 
               
               
                   
                   
                 Ph-6-H), 7.55 (d, 1H, Ph-4-H, J = 8.4 Hz), 7.65 (d, 1H, Ph-3-H, 
               
               
                   
                   
                 J = 8.4 Hz). 
               
               
                 6 
                 49 
                 m.p. 220-222° C. 7.04 (d, 1H, Ph-6-H, J = 8.7 Hz), 7.07 (s, 1H, 
               
               
                   
                   
                 NH), 8.20 (dd, 1H, Ph-5-H,  3 J = 9.0 Hz,  4 J = 2.7 Hz), 8.42 (d, 1H, 
               
               
                   
                   
                 Ph-3-H, J = 2.7 Hz). 
               
               
                 6 
                 77 
                 m.p. 200-202° C. δ (CDCl 3 ): 2.27 (s, 3H, Ph-2-CH 3 ), 6.86 (s, 1H, 
               
               
                   
                   
                 NH), 7.07 (d, 1H, Ph-6-H, J = 8.4 Hz), 7.23 (dd, 1H, Ph-5-H, 
               
               
                   
                   
                   3 J = 8.4 Hz,  4 J = 2.1 Hz), 7.33 (s, 1H, Ph-3-H). 
               
               
                 6 
                 78 
                 m.p. 140-142° C. δ (CDCl 3 ): 2.35 (s, 3H, CH 3 ), 6.99 (s, 1H, NH), 
               
               
                   
                   
                 7.08 (d, 1H, Ph-6-H, J = 8.1 Hz), 7.19-7.25 (m, 1H, Ph-5-H), 7.46 (d, 
               
               
                   
                   
                 1H, Ph-4-H, J = 8.7 Hz). 
               
               
                 6 
                 80 
                 m.p. 198-200° C. δ (CDCl 3 ): 2.23 (s, 3H, CH 3 ), 2.34 (s, 3H, 
               
               
                   
                   
                 CH 3 ), 6.95 (s, 1H, NH), 6.95 (s, 1H, Ph-6-H), 7.13-7.22 (m, 2H, 
               
               
                   
                   
                 Ph-3,4-2H). 
               
               
                 6 
                 83 
                 m.p. 204-205° C. δ (CDCl 3 ): 2.36 (s, 3H, COOCH 3 ), 3.92 (s, 3H, 
               
               
                   
                   
                 Ph-3-CH 3 ), 6.85 (s, 1H, NH), 7.12 (d, 1H, Ph-5-1H, J = 8.4 Hz), 
               
               
                   
                   
                 7.92 (d, 1H, Ph-6-1H, J = 8.4 Hz), 8.02 (s, 1H, Ph-2-1H). 
               
               
                 6 
                 84 
                 m.p. 216-218° C. δ (CDCl 3 ): 2.16 (s, 3H, CH 3 ), 3.89 (s, 3H, 
               
               
                   
                   
                 COOCH 3 ), 7.39 (t, 1H, Ph-4-H, J = 7.8 Hz), 7.51 (d, 1H, Ph-5-H, 
               
               
                   
                   
                 J = 7.8 Hz), 7.93 (d, 1H, Ph-3-H, J = 7.8 Hz). 
               
               
                 6 
                 85 
                 m.p. 242-243° C. δ (CDCl 3 ): 7.07 (s, 1H, NH), 7.25 (d, 1H, 
               
               
                   
                   
                 Ph-6-H, J = 2.1 Hz), 7.42 (d, 1H, Ph-2-H, J = 2.4 Hz), 7.83 (d, 1H, 
               
               
                   
                   
                 Ph-5-H, J = 8.4 Hz). 
               
               
                 6 
                 87 
                 m.p. 232-234° C. δ (CDCl 3 ): 6.94 (d, 1H, Ph-6-H, J = 9.3 Hz), 
               
               
                   
                   
                 7.58 (dd, 1H, Ph-5-H,  3 J = 9.0 Hz,  4 J = 2.7 Hz), 8.26 (d, 1H, Ph-3-H, 
               
               
                   
                   
                 J = 2.7 Hz), 9.36 (s, 1H, NH). 
               
               
                 6 
                 88 
                 m.p. 236-238° C. δ (DMSO): 7.02 (dd, 1H, Ph-6-H,  3 J = 9.6 Hz, 
               
               
                   
                   
                   4 J = 2.7 Hz), 8.32 (dd, 1H, Ph-5-H,  3 J = 9.3 Hz,  4 J = 2.7 Hz), 8.63 (d, 
               
               
                   
                   
                 1H, Ph-3-H, J = 2.7 Hz). 
               
               
                 6 
                 95 
                 m.p. 201-203° C. δ (CDCl 3 ): 6.91 (s, 1H, NH), 7.72 (s, 2H, 
               
               
                   
                   
                 Ph-3,5-2H). 
               
               
                 6 
                 98 
                 m.p. 259-261° C. δ (CDCl 3 ): 6.91 (s, 1H, NH), 7.74 (s, 2H, 
               
               
                   
                   
                 Ph-3,5-2H). 
               
               
                 6 
                 103 
                 m.p. 267-269° C. δ (CDCl 3 ): 7.28-7.30 (m, 1H, NHPh-4-H), 
               
               
                   
                   
                 7.40 t, 2H, NHPh-3,5-2H, J = 6.9 Hz), δ = 7.62 (d, 2H, NHPh-2,6-2H, 
               
               
                   
                   
                 J = 7.8 Hz), δ = 7.89-7.95 (m, 2H, NHCOPh-2,6-2H). 
               
               
                 6 
                 107 
                 m.p. 232-234° C. δ (CDCl 3 ): 2.43 (s, 3H, Ph—CH 3 ), 6.86 (s, 1H, 
               
               
                   
                   
                 NH), 8.14 (s, 1H, Ph-5-1H), 8.26 (s, 1H, Ph-3-1H). 
               
               
                 6 
                 108 
                 m.p. 196-198° C. δ (CDCl 3 ): 2.55 (s, 3H, CH 3 ), 6.99 (s, 1H, NH), 
               
               
                   
                   
                 7.04 (d, 1H, Ph-6-H, J = 8.4 Hz), 7.36 (d, 1H, Ph-5-H, J = 8.4 Hz). 
               
               
                 6 
                 109 
                 m.p. 194-196° C. δ (CDCl 3 ): 6.96 (s, 1H, NH), 7.67 (d, 1H, 
               
               
                   
                   
                 Ph-5-H, J = 2.1 Hz), 7.77 (d, 1H, Ph-3-H, J = 2.4 Hz). 
               
               
                 6 
                 110 
                 m.p. 197-199° C. 6.86 (s, 1H, NH), 8.05 (dd, 1H, Ph-5-H, 
               
               
                   
                   
                   3 J = 9.9 Hz,  4 J = 2.7 Hz), 8.28 (d, 1H, Ph-3-H, J = 2.4 Hz). 
               
               
                 6 
                 113 
                 m.p. 248-250° C. δ (CDCl 3 ): 6.95 (s, 1H, NH), 8.37 (d, 1H, 
               
               
                   
                   
                 Ph-3-H, J = 2.7 Hz), 8.49 (d, 1H, Ph-5-H, J = 2.4 Hz). 
               
               
                 6 
                 114 
                 m.p. 247-249° C. δ (CDCl 3 ): 6.96 (s, 1H, NH), 8.51 (s, 2H, 
               
               
                   
                   
                 Ph-3,5-2H). 
               
               
                 6 
                 134 
                 m.p. 176-178° C. δ (CDCl 3 ): 1.15-1.27 (m, 6H, CH 3 ), 2.49 (q, 
               
               
                   
                   
                 4H, CH 2 , J = 7.5 Hz), 6.98 (s, 1H, NH), 7.14 (d, 1H, Ph-5-H, 
               
               
                   
                   
                 J = 8.4 Hz), 7.47 (d, 1H, Ph-3-H, J = 8.4 Hz). 
               
               
                 6 
                 152 
                 m.p. 222-223° C. δ (CDCl 3 ): 2.22 (s, 3H, CH 3 ), 2.34 (s, 3H, CH 3 ), 
               
               
                   
                   
                 6.88 (s, 1H, NH), 7.00 (s, 1H, Ph-6-H), 7.30 (s, 1H, Ph-3-H). 
               
               
                 6 
                 176 
                 m.p. 260-262° C. δ (CDCl 3 ): 2.06 (s, 3H, CH 3 ), 2.98 (d, 3H, 
               
               
                   
                   
                 NHCH 3 , J = 4.8 Hz), 6.38 (s, 1H, CONH), 7.67 (s, 2H, Ph-3,5-2H), 
               
               
                   
                   
                 9.38 (s, 1H, NH). 
               
               
                 6 
                 178 
                 m.p. 240-242° C. δ (CDCl 3 ): 2.08 (s, 3H, CH 3 ), 2.93 (d, 3H, 
               
               
                   
                   
                 NCH 3 , J = 5.1 Hz), 6.22 (s, 1H, CONH), 7.35-7.38 (m, 2H, 
               
               
                   
                   
                 Ph-3,5-2H), 8.59 (s, 1H, NH). 
               
               
                 6 
                 180 
                 m.p. 180-182° C. δ (CDCl 3 ): 2.69 (s, 3H, CH 3 ), 7.12 (s, 1H, NH), 
               
               
                   
                   
                 7.24-7.68 (m, 4H, Ph). 
               
               
                 6 
                 206 
                 m.p. 156-158° C. δ (CDCl 3 ): 2.51 (s, 3H, CH 3 ), 8.67 (s, 1H, Ph), 
               
               
                   
                   
                 8.89 (s, 1H, NH). 
               
               
                 9 
                 8 
                 Yellow oil. δ (CDCl 3 ): 1.13-1.21 (m, 6H, CH 3 ), 3.46 (q, 4H, 
               
               
                   
                   
                 CH 2 , J = 7.2 Hz), 6.90 (s, 1H, NH), 7.13 (t, 2H, Ph-2,6-2H, 
               
               
                   
                   
                 J = 7.5 Hz), 7.31 (d, 1H, Ph-4-H, J = 7.5 Hz), 7.42 (t, 2H, 
               
               
                   
                   
                 Ph-3,5-2H, J = 7.2 Hz). 
               
               
                 10 
                 99 
                 m.p. 127-129° C. δ (CDCl 3 ): 3.22 (s, 6H, CH 3 ), 6.85 (s, 1H, NH), 
               
               
                   
                   
                 8.32 (s, 2H, Ph-3,5-2H). 
               
               
                 12 
                 99 
                 m.p. 198-200° C. δ (CDCl 3 ): 4.25 (s, 3H, CH 3 ), 6.87 (s, 1H, NH), 
               
               
                   
                   
                 8.32 (s, 2H, Ph-3,5-2H). 
               
               
                 14 
                 4 
                 m.p. 142-144° C. δ (CDCl 3 ): 4.14 (s, 3H, OCH 3 ), 4.17 (t, 3H, 
               
               
                   
                   
                 OCH 3 , J = 4.2 Hz), 6.91 (s, 1H, Ph—NH—Ph), 7.18 (d, 2H, 
               
               
                   
                   
                 Ph-2,6-2H, J = 7.8 Hz), 7.32 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.42 (t, 
               
               
                   
                   
                 2H, Ph-3,5-2H, J = 7.5 Hz). 
               
               
                 16 
                 2 
                 m.p. 176-178° C. δ (CDCl 3 ): 3.26 (d, 3H, NCH 3 , J = 8.7 Hz), 
               
               
                   
                   
                 3.37 (d, 3H, NCH 3  J = 8.1 Hz), 5.04 (br, 1H, Ph—NH—C), 5.26 (br, 1H, 
               
               
                   
                   
                 Ph—NH—C), 6.35 (s, 1H, Ph—NH—Ph), 7.04 (d, 2H, Ph-2,6-2H, 
               
               
                   
                   
                 J = 8.1 Hz), 7.14 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.35 (t, 2H, 
               
               
                   
                   
                 Ph-3,5-2H, J = 7.5 Hz). 
               
               
                 22 
                 11 
                 m.p. 158-160° C. δ (CDCl 3 ): 2.10 (s, 3H), 6.83 (d, 4H), 7.12 (m, 
               
               
                   
                   
                 2H), 7.34 (m, 4H), 8.56 (s, 1H). 
               
               
                 22 
                 22 
                 m.p. 172-174° C. δ (DMSO): 2.34 (s, 3H), 6.83 (d, 2H), 8.06 (d, 
               
               
                   
                   
                 2H), 8.64 (s, 1H), 9.49 (s, 1H). 
               
               
                 22 
                 23 
                 m.p. 184-186° C. δ (CDCl 3 ): 2.22 (s, 3H), 6.87 (d, 2H), 7.62 (d, 
               
               
                   
                   
                 2H), 8.66 (s, 1H), 8.93 (s, 1H). 
               
               
                 22 
                 24 
                 m.p. 91-94° C. δ (CDCl 3 ): 2.14 (s, 3H), 6.91 (d, 2H), 7.21 (d, 2H), 
               
               
                   
                   
                 8.71 (s, 1H), 9.20 (s, 1H). 
               
               
                 22 
                 31 
                 m.p. 136-138° C. δ (CDCl 3 ): 2.12 (s, 3H), 7.21 (m, 2H), 7.26 (m, 
               
               
                   
                   
                 1H), 8.72 (s, 1H), 9.00 (s, 1H). 
               
               
                 22 
                 47 
                 m.p. 106-108° C. δ (CDCl 3 ): 2.22 (s, 3H), 6.55 (d, 1H), 7.43 (d, 
               
               
                   
                   
                 1H), 7.75 (s, 1H), 8.65 (s, 1H), 8.87 (s, 1H). 
               
               
                 22 
                 48 
                 m.p. 110-112° C. δ (CDCl 3 ): 2.03 (s, 3H), 2.50 (s, 3H), 6.50 (d, 
               
               
                   
                   
                 1H), 7.05 (t, 1H), 7.24 (d, 1H), 8.73 (s, 1H), 9.06 (s, 1H). 
               
               
                 22 
                 50 
                 m.p. 191-193° C. δ (CDCl 3 ): 2.29 (s, 3H), 6.48 (d, 1H), 8.06 (d, 
               
               
                   
                   
                 1H), 8.41 (s, 1H), 8.62 (s, 1H), 8.79 (s, 1H). 
               
               
                 22 
                 56 
                 m.p. 146-148° C. δ (CDCl 3 ): 1.86 (s, 3H), 2.40 (s, 3H), 7.18 (m, 
               
               
                   
                   
                 2H), 7.28 (m, 1H), 8.80 (s, 1H), 9.52 (s, 1H). 
               
               
                 22 
                 58 
                 m.p. 133-135° C. δ (CDCl 3 ): 2.03 (s, 3H), 2.50 (s, 3H), 6.53 (d, 
               
               
                   
                   
                 1H), 7.06 (t, 1H), 7.21 (d, 1H), 8.74 (s, 1H), 9.08 (s, 1H). 
               
               
                 22 
                 61 
                 m.p. 206-208° C. δ (CDCl 3 ): 2.25 (s, 3H), 6.48 (d, 1H), 7.47 (d, 
               
               
                   
                   
                 1H), 7.77 (s, 1H), 8.62 (s, 1H), 8.80 (s, 1H). 
               
               
                 22 
                 63 
                 m.p. 259-261° C. δ (CDCl 3 ): 2.38 (s, 3H), 6.54 (d, 1H), 7.70 (d, 
               
               
                   
                   
                 1H), 8.50 (s, 1H), 8.62 (s, 1H), 10.51 (s, 1H). 
               
               
                 22 
                 80 
                 m.p. 121-123° C. δ (CDCl 3 ): 2.02 (s, 3H), 2.40 (s, 3H), 6.53 (d, 
               
               
                   
                   
                 1H), 7.10 (d, 1H), 7.27 (s, 1H), 8.74 (s, 1H), 9.03 (s, 1H). 
               
               
                 22 
                 86 
                 oil. δ (DMSO): 2.33 (s, 3H), 6.92 (d, 1H), 7.26 (s, 1H), 7.78 (d, 
               
               
                   
                   
                 1H), 8.63 (s, 1H), 9.54 (s, 1H). 
               
               
                 22 
                 88 
                 m.p. 204-205° C. δ (CDCl 3 ): 2.31 (s, 3H), 6.48 (d, 1H), 7.43 (d, 
               
               
                   
                   
                 1H), 8.26 (s, 1H), 8.54 (s, 1H), 10.36 (s, 1H). 
               
               
                 22 
                 89 
                 m.p. 185-186° C. δ (CDCl 3 ): 2.41 (s, 3H), 6.56 (d, 1H), 8.31 (d, 
               
               
                   
                   
                 1H), 8.52 (s, 1H), 9.23 (s, 1H), 10.59 (s, 1H). 
               
               
                 22 
                 93 
                 m.p. 148-150° C. δ (CDCl 3 ): 2.12 (s, 3H), 7.04 (d, 2H), 8.70 (s, 
               
               
                   
                   
                 1H), 8.87 (s, 1H). 
               
               
                 22 
                 94 
                 m.p. 154-156° C. δ (CDCl 3 ): 2.21 (s, 3H), 7.20 (m, 1H), 7.80 (m, 
               
               
                   
                   
                 1H), 8.59 (s, 1H), 9.94 (s, 1H). 
               
               
                 22 
                 95 
                 m.p. 140-142° C. δ (CDCl 3 ): 2.17 (s, 3H), 7.19 (d, 2H), 8.71 (s, 
               
               
                   
                   
                 1H), 8.94 (s, 1H). 
               
               
                 22 
                 97 
                 m.p. 142-143° C. δ (CDCl 3 ): 2.20 (s, 3H), 6.59 (s, 1H), 7.58 (s, 
               
               
                   
                   
                 1H), 8.67 (s, 1H), 8.80 (s, 1H). 
               
               
                 22 
                 98 
                 m.p. 160-162° C. δ (CDCl 3 ): 1.95 (s, 3H), 7.41 (s, 2H), 8.72 (s, 
               
               
                   
                   
                 1H), 9.19 (s, 1H). 
               
               
                 22 
                 104 
                 m.p. 180-182° C. δ (CDCl 3 ): 1.99 (s, 3H), 7.69 (s, 2H), 8.67 (s, 
               
               
                   
                   
                 1H), 9.00 (s, 1H). 
               
               
                 22 
                 106 
                 m.p. 169-171° C. δ (CDCl 3 ): 2.32 (s, 3H), 6.42 (s, 1H), 8.20 (s, 
               
               
                   
                   
                 1H), 8.60 (s, 1H), 8.62 (s, 1H). 
               
               
                 22 
                 107 
                 m.p. 132-134° C. δ (CDCl 3 ): 1.95 (s, 3H), 3.96 (s, 3H), 8.05 (s, 
               
               
                   
                   
                 2H), 8.70 (s, 1H), 9.13 (s, 1H). 
               
               
                 22 
                 116 
                 m.p. 216-219° C. δ (CDCl 3 ): 2.30 (s, 3H), 7.88 (s, 2H), 8.48 (s, 
               
               
                   
                   
                 1H), 8.85 (s, 1H). 
               
               
                 22 
                 118 
                 m.p. 169-171° C. δ (CDCl 3 ): 2.26 (s, 3H), 8.50 (d, 2H), 8.99 (s, 
               
               
                   
                   
                 1H), 10.14 (s, 1H). 
               
               
                 22 
                 119 
                 m.p. 160-161° C. δ (CDCl 3 ): 2.13 (s, 3H), 2.54 (s, 3H), 6.40 (d, 
               
               
                   
                   
                 1H), 7.19 (d, 1H), 8.68 (s, 1H), 8.96 (s, 1H). 
               
               
                 22 
                 122 
                 m.p. 135-137° C. δ (CDCl 3 ): 2.16 (s, 3H), 7.95 (dd, 1H), 8.26 (t, 
               
               
                   
                   
                 1H), 8.63 (s, 1H), 8.82 (s, 1H). 
               
               
                 22 
                 123 
                 m.p. 151-153° C. δ (CDCl 3 ): 1.99 (s, 3H), 8.31 (d, 1H), 8.47 (d, 
               
               
                   
                   
                 1H), 8.66 (s, 1H), 9.00 (s, 1H). 
               
               
                 22 
                 124 
                 m.p. 96-97° C. δ (CDCl 3 ): 2.21 (s, 3H), 5.08 (m, 1H), 6.59 (s, 1H), 
               
               
                   
                   
                 7.49 (s, 1H), 8.66 (s, 1H), 8.78 (s, 1H). 
               
               
                 22 
                 125 
                 m.p. 192-194° C. δ (CDCl 3 ): 2.20 (s, 3H), 7.05 (s, 2H), 8.04 (s, 
               
               
                   
                   
                 1H), 8.22 (s, 1H), 9.07 (s, 1H), 9.43 (s, 1H). 
               
               
                 22 
                 126 
                 m.p. 125-127° C. δ (CDCl 3 ): 1.94 (s, 3H), 7.53 (s, 2H), 8.75 (s, 
               
               
                   
                   
                 1H), 9.29 (s, 1H). 
               
               
                 22 
                 129 
                 m.p. 151-154° C. δ (CDCl 3 ): 1.97 (s, 3H), 8.49 (s, 2H), 8.68 (s, 
               
               
                   
                   
                 1H), 9.03 (s, 1H). 
               
               
                 22 
                 130 
                 m.p. 172-175° C. δ (DMSO): 2.32 (s, 3H), 8.49 (s, 1H), 8.68 (s, 
               
               
                   
                   
                 2H), 9.50 (s, 1H). 
               
               
                 22 
                 133 
                 m.p. 131-132° C. δ (CDCl 3 ): 2.10 (s, 3H), 6.99 (t, 2H), 7.17 (m, 
               
               
                   
                   
                 1H), 8.72 (s, 1H), 8.98 (s, 1H). 
               
               
                 22 
                 139 
                 m.p. 158-161° C. δ (CDCl 3 ): 2.16 (s, 3H), 2.61 (s, 3H), 6.47 (d, 
               
               
                   
                   
                 1H), 7.67 (d, 1H), 8.69 (s, 1H), 8.85 (s, 1H). 
               
               
                 22 
                 140 
                 m.p. 137-139° C. δ (CDCl 3 ): 1.91 (s, 3H), 2.31 (s, 3H), 8.10 (s, 
               
               
                   
                   
                 1H), 8.21 (s, 1H), 8.73 (s, 1H), 9.20 (s, 1H). 
               
               
                 22 
                 152 
                 m.p. 160-162° C. δ (CDCl 3 ): 2.18 (s, 3H), 7.88 (d, 1H), 8.32 (d, 
               
               
                   
                   
                 1H), 8.55 (s, 1H), 9.97 (s, 1H). 
               
               
                 22 
                 163 
                 m.p. 241-243° C. δ (CDCl 3 ): 1.97 (s, 3H), 7.83 (s, 2H), 8.69 (s, 
               
               
                   
                   
                 1H), 9.11 (s, 1H). 
               
               
                 22 
                 164 
                 δ (CDCl 3 ): 1.94 (s, 3H), 3.03 (d, 3H), 7.78 (s, 2H), 8.70 (s, 1H), 
               
               
                   
                   
                 9.14 (s, 1H). 
               
               
                 22 
                 169 
                 m.p. 187-190° C. δ (CDCl 3 ): 2.18 (s, 3H), 8.23 (s, 2H), 8.57 (s, 
               
               
                   
                   
                 1H), 10.39 (s, 1H). 
               
               
                 22 
                 170 
                 oil. δ (CDCl 3 ): 2.27 (s, 3H), 8.52 (s, 1H), 9.09 (s, 2H), 10.93 (s, 
               
               
                   
                   
                 1H). 
               
               
                 22 
                 171 
                 m.p. 93-95° C. δ (CDCl 3 ): 2.19 (s, 3H), 8.14 (s, 2H), 8.56 (s, 1H), 
               
               
                   
                   
                 10.42 (s, 1H). 
               
               
                 22 
                 172 
                 m.p. 204-206° C. δ (DMSO): 2.32 (s, 3H), 7.03 (s, 1H), 8.73 (s, 
               
               
                   
                   
                 1H), 8.86 (s, 1H), 10.40 (s, 1H). 
               
               
                 22 
                 180 
                 m.p. 127-129° C. δ (CDCl 3 ): 2.36 (s, 3H), 6.55 (s, 1H), 8.40 (s, 
               
               
                   
                   
                 1H), 8.54 (s, 1H), 10.31 (s, 1H). 
               
               
                 22 
                 207 
                 m.p. 159-162° C. δ (CDCl 3 ): 2.16 (s, 3H), 8.23 (s, 1H), 8.63 (s, 
               
               
                   
                   
                 1H), 8.91 (s, 1H). 
               
               
                 22 
                 208 
                 m.p. 133-135° C. δ (CDCl 3 ): 2.07 (s, 3H), 7.70 (s, 1H), 8.69 (s, 
               
               
                   
                   
                 1H), 9.22 (s, 1H). 
               
               
                 23 
                 22 
                 m.p. 136-138° C. δ (CDCl 3 ): 2.22 (s, 3H), 6.70 (d, 2H), 7.41 (d, 
               
               
                   
                   
                 1H), 8.00 (d, 1H), 8.16 (d, 2H), 8.22 (s, 1H). 
               
               
                 23 
                 23 
                 m.p. 146-148° C. δ (CDCl 3 ): 2.19 (s, 3H), 6.70 (d, 2H), 7.36 (d, 
               
               
                   
                   
                 1H), 7.53 (d, 2H), 7.96 (d, 1H), 8.20 (s, 1H). 
               
               
                 23 
                 24 
                 m.p. 72-74° C. δ (CDCl 3 ): 2.12 (s, 3H), 6.75 (d, 2H), 7.12 (d, 2H), 
               
               
                   
                   
                 7.25 (d, 1H), 7.98 (d, 1H), 8.46 (s, 1H). 
               
               
                 23 
                 63 
                 m.p. 158-160° C. δ (CDCl 3 ): 2.30 (s, 3H), 6.47 (d, 1H), 7.59 (m, 
               
               
                   
                   
                 2H), 7.94 (d, 1H), 8.60 (s, 1H), 10.21 (s, 1H). 
               
               
                 23 
                 77 
                 m.p. 136-138° C. δ (CDCl 3 ): 2.22 (s, 3H), 6.75 (d, 1H), 7.03(s, 
               
               
                   
                   
                 1H), 7.45 (d, 1H), 7.67 (d, 1H), 7.99 (d, 1H), 8.16 (s, 1H). 
               
               
                 23 
                 80 
                 oil. δ (CDCl 3 ): 2.02 (s, 3H), 2.38 (s, 3H), 6.34 (d, 1H), 7.00 (d, 
               
               
                   
                   
                 1H), 7.18 (m, 2H), 7.98 (d, 1H), 8.30 (s, 1H). 
               
               
                 23 
                 97 
                 m.p. 112-114° C. δ (CDCl 3 ): 2.18 (s, 3H), 6.38 (s, 1H), 7.38 (d, 
               
               
                   
                   
                 1H), 7.50 (s, 1H), 7.97 (d, 1H), 8.11 (s, 1H). 
               
               
                 23 
                 101 
                 oil. δ (CDCl 3 ): 1.92 (s, 3H), 7.22 (d, 1H), 7.58 (s, 2H), 7.93 (d, 
               
               
                   
                   
                 1H), 8.39 (s, 1H). 
               
               
                 24 
                 47 
                 m.p. 138-140° C. δ (CDCl 3 ): 2.58 (s, 3H), 3.37 (s, 3H), 7.23 (d, 
               
               
                   
                   
                 1H), 7.48 (s, 1H), 7.57 (d, 1H), 8.08 (s, 1H). 
               
               
                 24 
                 170 
                 m.p. 140-142° C. δ (CDCl 3 ): 2.58 (s, 3H), 3.30 (s, 3H), 8.38 (s, 
               
               
                   
                   
                 1H), 8.57 (s, 2H). 
               
               
                 25 
                 105 
                 m.p. 134-136° C. δ (CDCl 3 ): 1.79 (s, 3H), 3.96 (s, 3H), 8.29 (s, 
               
               
                   
                   
                 2H), 8.74 (s, 1H), 9.18 (s, 1H). 
               
               
                 26 
                 105 
                 m.p. 132-134° C. δ (CDCl 3 ): 2.11 (s, 3H), 2.39 (s, 3H), 8.29 (s, 
               
               
                   
                   
                 2H), 8.47 (s, 1H), 8.95 (s, 1H). 
               
               
                 27 
                 164 
                 m.p. 216-218° C. δ (CDCl 3 ): 1.56 (s, 3H), 3.04 (m, 6H), 7.80 (s, 
               
               
                   
                   
                 2H), 8.18 (s, 1H), 9.13 (s, 1H), 9.58 (s, 1H). 
               
               
                 28 
                 105 
                 m.p. 178-180° C. δ (CDCl 3 ): 1.71 (s, 3H), 2.86 (s, 6H), 8.29 (s, 
               
               
                   
                   
                 2H), 8.66 (s, 1H), 9.45 (s, 1H). 
               
               
                 30 
                 101 
                 m.p. 155-157° C. δ (CDCl 3 ): 1.90 (s, 3H), 7.66 (s, 2H), 8.21 (s, 
               
               
                   
                   
                 1H), 8.98 (s, 1H), 9.19 (s, 1H). 
               
               
                 30 
                 104 
                 m.p. 183-185° C. δ (CDCl 3 ): 1.93 (s, 3H), 7.68 (s, 2H), 8.23 (d, 
               
               
                   
                   
                 1H), 8.94 (d, 1H), 9.03 (s, 1H). 
               
               
                 30 
                 120 
                 m.p. 175-177° C. δ (CDCl 3 ): 2.00 (s, 3H), 7.54 (d, 1H), 7.71 (d, 
               
               
                   
                   
                 1H), 8.28 (d, 1H), 8.96 (d, 1H), 9.02 (s, 1H). 
               
               
                 30 
                 122 
                 m.p. 108-110° C. δ (CDCl 3 ): 2.11 (s, 3H), 7.95 (dd, 1H), 8.26 (d, 
               
               
                   
                   
                 1H), 8.31 (d, 1H), 8.79 (s, 1H), 8.92 (d, 1H). 
               
               
                   
               
             
          
         
       
     
     Cell Viability Assay 
     Example 22 
     In Vitro Cell Inhibition Assay (MTT Method) 
     The human cancer cell lines used for this assay were lung cancer A549 and leukemia HL-60. 
     The concentrations of compounds used for this assay were 0.01, 0.1, 1, 10, 100 μM. Based on in vitro cell culture, we use the MTT assay to detect the inhibitory rate of each compound. 
     The A549 or HL-60 cells were picked up from cell incubator, after washed for twice using PBS, cells were digested by 0.25% trypsin, and then add medium to terminate the digestion. After cells were collected using centrifuge and re-suspended, count cells under inverted microscope and add medium to make a density was 5×10 4  cells/mL. After 100 μL aliquots were added to each well of 96-well microtiter plates, cells were cultured in 5% incubator for overnight at 37° C., then the different concentration compounds were added to each well. After incubation for 48 h, MTT solution was added to each well and plates were then incubated for 4 h. The MTT tetrazolium was reduced to formazan by living cells. Then the formazan crystals were dissolved though adding DMSO to each well. The absorbance was read at 570 nm with a microplate reader. 
     Part of the test results are as follows: 
     
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 31 
               
             
             
               
                   
               
               
                 Proliferation inhibitory effect of the compounds on A549 cell 
               
               
                 (% of Control) 
               
             
          
           
               
                   
                 Compounds 
                 Concentration (μM) 
               
             
          
           
               
                   
                 No. 
                 100 
                 10 
                 1 
                 0.1 
                 0.01 
               
               
                   
                   
               
             
          
           
               
                   
                 6-1  
                 19.8 
                 20.4 
                 16.9 
                 12.1 
                 13.1 
               
               
                   
                 6-23 
                 93.8 
                 93.7 
                 2.5 
                 −1.8 
                 −0.8 
               
               
                   
                 6-35 
                 92.7 
                 58.6 
                 1.0 
                 −0.8 
                 0.5 
               
               
                   
                 6-39 
                 92.6 
                 24.9 
                 19.6 
                 18.8 
                 18.3 
               
               
                   
                 6-41 
                 92.0 
                 84.0 
                 13.1 
                 0.7 
                 3.8 
               
               
                   
                 6-93 
                 98.2 
                 80.3 
                 74.8 
                 39.4 
                 12.1 
               
               
                   
                 6-98 
                 93.2 
                 90.1 
                 11.7 
                 −0.7 
                 −2.5 
               
               
                   
                 6-99 
                 86.3 
                 83.6 
                 55.0 
                 0 
                 0 
               
               
                   
                  6-113 
                 93.7 
                 75.6 
                 2.6 
                 2.9 
                 9.2 
               
               
                   
                  6-114 
                 94.9 
                 82.1 
                 11.5 
                 2.8 
                 10.1 
               
               
                   
                 22-33  
                 90.3 
                 78.7 
                 61.3 
                 −1.1 
                 −1.6 
               
               
                   
                 22-93  
                 91.4 
                 73.7 
                 −0.2 
                 −1.8 
                 −2.2 
               
               
                   
                 22-101 
                 97.5 
                 66.4 
                 19.1 
                 21.4 
                 13.7 
               
               
                   
                 22-105 
                 89.8 
                 80.6 
                 49.9 
                 8.8 
                 16 
               
               
                   
                 22-120 
                 92.1 
                 86.8 
                 9.8 
                 0 
                 0.8 
               
               
                   
                 22-121 
                 89.5 
                 51.2 
                 9.9 
                 12.4 
                 6.2 
               
               
                   
                 22-153 
                 85.2 
                 60.6 
                 14.7 
                 0 
                 3.7 
               
               
                   
                 22-208 
                 91.3 
                 83.2 
                 2.4 
                 −1.2 
                 −1.0 
               
               
                   
                 25-105 
                 93.7 
                 78.0 
                 0.9 
                 2.2 
                 3.1 
               
               
                   
                 28-105 
                 89.6 
                 54.9 
                 2.7 
                 5.3 
                 4.1 
               
               
                   
                 29-105 
                 91.9 
                 94.2 
                 72.7 
                 −0.5 
                 −0.2 
               
               
                   
                 30-104 
                 91.8 
                 78.4 
                 −0.1 
                 1.1 
                 2.4 
               
               
                   
                 30-120 
                 92.0 
                 84.0 
                 −0.7 
                 −0.9 
                 −1.5 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 32 
               
             
             
               
                   
               
               
                 Proliferation inhibitory effect of the compounds on HL-60 cells 
               
               
                 (% of Control) 
               
             
          
           
               
                   
                 Compounds 
                 Concentration (μM) 
               
             
          
           
               
                   
                 No. 
                 100 
                 10 
                 1 
                 0.1 
                 0.01 
               
               
                   
                   
               
             
          
           
               
                   
                 6-1  
                 61.9 
                 63.9 
                 18.8 
                 10.4 
                 11.5 
               
               
                   
                 6-3  
                 94.5 
                 72.2 
                 −2.1 
                 −6.3 
                 −7.1 
               
               
                   
                 6-10 
                 77.1 
                 78.5 
                 9.8 
                 16.1 
                 21.8 
               
               
                   
                 6-23 
                 90.6 
                 93.2 
                 23.1 
                 10.8 
                 2.3 
               
               
                   
                 6-35 
                 89.9 
                 72.3 
                 −1.8 
                 −5.0 
                 −8.3 
               
               
                   
                 6-39 
                 80.8 
                 78.5 
                 31.0 
                 14.7 
                 11.9 
               
               
                   
                 6-41 
                 87.9 
                 86.5 
                 7.8 
                 3.9 
                 6.5 
               
               
                   
                 6-93 
                 74.8 
                 72.3 
                 70.7 
                 51.8 
                 0 
               
               
                   
                 6-98 
                 95.1 
                 91.7 
                 30.0 
                 10.1 
                 −2.5 
               
               
                   
                 6-99 
                 54.8 
                 56.5 
                 60.2 
                 34.2 
                 8.6 
               
               
                   
                  6-109 
                 94.4 
                 52.4 
                 2.9 
                 2.2 
                 0.1 
               
               
                   
                  6-113 
                 93.1 
                 85.4 
                 9.3 
                 8.8 
                 −3.8 
               
               
                   
                  6-114 
                 93.2 
                 87.5 
                 20.7 
                 10.0 
                 −0.4 
               
               
                   
                  6-205 
                 91.9 
                 59.5 
                 5.8 
                 12.6 
                 −3.4 
               
               
                   
                 22-24  
                 94.3 
                 82.4 
                 −9.3 
                 −16.7 
                 −22.4 
               
               
                   
                 22-33  
                 81.2 
                 66.2 
                 54.3 
                 −1.8 
                 −4.9 
               
               
                   
                 22-61  
                 89.8 
                 85.7 
                 11.0 
                 7.8 
                 5.2 
               
               
                   
                 22-88  
                 94.1 
                 79.1 
                 −24.6 
                 −32.9 
                 −35.2 
               
               
                   
                 22-93  
                 95.4 
                 70.4 
                 6.8 
                 −7.1 
                 −3.6 
               
               
                   
                 22-95  
                 95.4 
                 76.0 
                 32.6 
                 −4.0 
                 0.3 
               
               
                   
                 22-98  
                 91.0 
                 77.7 
                 9.5 
                 1.3 
                 −7.3 
               
               
                   
                 22-101 
                 64.7 
                 73.4 
                 48.6 
                 5.5 
                 8.3 
               
               
                   
                 22-104 
                 94.0 
                 60.5 
                 −2.1 
                 −7.3 
                 4.1 
               
               
                   
                 22-105 
                 53.8 
                 70.4 
                 71.1 
                 31.7 
                 27.2 
               
               
                   
                 22-107 
                 94.4 
                 65.4 
                 −7.0 
                 −9.3 
                 2.8 
               
               
                   
                 22-120 
                 61.0 
                 63.1 
                 19.7 
                 20.5 
                 9.6 
               
               
                   
                 22-121 
                 61.2 
                 73.6 
                 47.6 
                 12.5 
                 13 
               
               
                   
                 22-122 
                 94.6 
                 57.2 
                 11.7 
                 −1.9 
                 6.3 
               
               
                   
                 22-153 
                 65.8 
                 73.4 
                 59.6 
                 7.3 
                 12.9 
               
               
                   
                 22-207 
                 90.5 
                 61.9 
                 0.4 
                 −3.6 
                 7.3 
               
               
                   
                 22-208 
                 91.2 
                 91.2 
                 28.9 
                 −14.0 
                 −8.0 
               
               
                   
                 25-105 
                 88.0 
                 80.2 
                 20.0 
                 4.4 
                 3.1 
               
               
                   
                 26-105 
                 88.0 
                 80.2 
                 20.0 
                 4.4 
                 3.1 
               
               
                   
                 28-105 
                 77.2 
                 88.4 
                 13.3 
                 −3.7 
                 4.9 
               
               
                   
                 29-105 
                 91.5 
                 95.1 
                 94.7 
                 70.2 
                 11.2 
               
               
                   
                 30-101 
                 80.7 
                 57.3 
                 −0.3 
                 −14.2 
                 −6.4 
               
               
                   
                 30-104 
                 93.3 
                 88.0 
                 65.3 
                 31.6 
                 21.8 
               
               
                   
                 30-105 
                 89.0 
                 85.6 
                 80.6 
                 43.6 
                 −6.8 
               
               
                   
                 30-120 
                 95.7 
                 95.9 
                 70.6 
                 39.2 
                 23.6 
               
               
                   
                 30-122 
                 82.4 
                 61.3 
                 18.0 
                 7.4 
                 10.7 
               
               
                   
                   
               
             
          
         
       
     
     Example 23 
     In Vitro Cell Inhibition Assay Using the Cell Counting Kit-8(CCK-8) Method 
     The human cancer cell lines used for this assay were: non-small cell lung cancer A549, NCI-H1650 and NCI-H358, leukemia HL-60, CCRF-CEM and MOLT-4, colon cancer HT-29 and COLO-205, pancreatic cancer BXPC-3, hepatocarcinoma SK-HEP-1, cervical cancer Hela, bladder cancer T24, prostate cancer DU-145 and PC-3, osteosarcoma MG-63, breast cancer MDA-MB-231, intracranial malignant melanoma A375, glioma U251, nasopharyngeal carcinoma CNE. 
     The concentrations of compounds used for this assay were 0.01, 0.1, 1, 10, 100 μM. Based on in vitro cell culture, we use the CCK-8 assay to detect the inhibitory rate of each compound. 
     The non-small cell lung cancer A549, NCI-H1650 and NCI-H358, colon cancer HT-29 and COLO-205, pancreatic cancer BXPC-3, hepatocarcinoma SK-HEP-1, cervical cancer Hela, bladder cancer T24, prostate cancer DU-145 and PC-3, osteosarcoma MG-63, breast cancer MDA-MB-231, intracranial malignant melanoma A375, glioma U251, nasopharyngeal carcinoma CNE were picked up from cell incubator. After the cell culture flasks gently shaking, culture fluid was discarded in clean bench. Then washed cells for twice using PBS, and add 0.25% trypsin to digest, when the cells were turning round, add medium to terminate digestion. Cells were collected and transferred to centrifuge tube. For the non-adherent cells HL-60, CCRF-CEM and MOLT-4, cell flasks were picked up from incubator and then transferred to the centrifuge tubes directly. After cells were collected using centrifuge at 1000 rpm/min for 5 min, the fluid was discarded. Then cells were washed for one time by PBS, discard fluid. Then add some medium, count cells under inverted microscope using blood cell counting plate, according the counting number to making the density of adherent cell was 1×10 5  cells/mL, the non-adherent cell was 2×10 5  cells/mL (the volumes of HL-60, CCRF-CEM, MOLT-4 are smaller than non-adherent cells, these cells added to each well was much more higher). Add 50 μL aliquots to each well of 96-well plates (the density of adherent cells was 5000 cells/well, non-adherent cells was 10000 cells/well). Blank control, Negative control, blank control with compounds and positive control wells were grouped, and three replicate wells were used for each data point in the experiments. Then the cells were cultured in 5% incubator for overnight at 37° C., Then the different concentration compounds were added to each well. After incubation for 48 h, according to the manufacturer&#39;s instructions, CCK-8 reagent (10 μl) was added and incubation was continued for a further 2-4 h. The absorbance (A) of each well was read at 450 nm using a plate reader. 
     
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 33 
               
             
             
               
                   
               
               
                 Proliferation inhibitory effect of the compounds on A549 cells 
               
               
                 (% of Control) 
               
             
          
           
               
                   
                 Compounds 
                 Concentration (μM) 
               
             
          
           
               
                   
                 No. 
                 100 
                 10 
                 1 
                 0.1 
                 0.01 
               
               
                   
                   
               
               
                   
                 6-24 
                 87.36 
                 60.31 
                 31.44 
                 24.27 
                 22.06 
               
               
                   
                 6-25 
                 81.32 
                 55.87 
                 17.11 
                 18.59 
                 15.66 
               
               
                   
                 6-47 
                 99.91 
                 55.57 
                 53.58 
                 49.86 
                 42.56 
               
               
                   
                 6-93 
                 98.18 
                 87.64 
                 70.04 
                 19.35 
                 14.77 
               
               
                   
                 6-95 
                 98.69 
                 97.88 
                 78.63 
                 56.27 
                 39.65 
               
               
                   
                 6-100 
                 89.94 
                 57.45 
                 52.15 
                 50.53 
                 43.98 
               
               
                   
                 6-111 
                 99.83 
                 80.03 
                 53.14 
                 29.42 
                 23.15 
               
               
                   
                 6-112 
                 99.26 
                 89.34 
                 76.90 
                 47.20 
                 46.52 
               
               
                   
                 6-201 
                 83.86 
                 60.23 
                 26.90 
                 19.63 
                 14.31 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 34 
               
             
             
               
                   
               
               
                 Proliferation inhibitory effect of the compounds on HL-60 cells 
               
               
                 (% of Control) 
               
             
          
           
               
                   
                 Compounds 
                 Concentration (μM) 
               
             
          
           
               
                   
                 No. 
                 100 
                 10 
                 1 
                 0.1 
                 0.01 
               
               
                   
                   
               
             
          
           
               
                   
                 6-24 
                 95.11 
                 56.72 
                 48.39 
                 17.55 
                 0.00 
               
               
                   
                 6-25 
                 84.30 
                 92.02 
                 84.06 
                 42.54 
                 11.52 
               
               
                   
                 6-43 
                 78.53 
                 73.80 
                 38.45 
                 31.60 
                 23.65 
               
               
                   
                 6-45 
                 80.30 
                 52.09 
                 39.89 
                 27.78 
                 0.00 
               
               
                   
                 6-47 
                 98.51 
                 83.33 
                 41.47 
                 34.70 
                 7.02 
               
               
                   
                 6-93 
                 93.71 
                 87.80 
                 82.05 
                 44.96 
                 30.19 
               
               
                   
                 6-95 
                 96.40 
                 94.99 
                 94.76 
                 43.28 
                 0.00 
               
               
                   
                 6-100 
                 97.42 
                 49.85 
                 39.47 
                 26.90 
                 14.24 
               
               
                   
                 6-111 
                 99.28 
                 95.16 
                 79.31 
                 41.52 
                 13.70 
               
               
                   
                 6-112 
                 96.45 
                 97.63 
                 91.55 
                 59.46 
                 48.31 
               
               
                   
                 6-201 
                 98.14 
                 86.76 
                 75.70 
                 48.61 
                 40.59 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 35 
               
             
             
               
                   
               
               
                 The half maximal inhibitory concentration (IC50) of the compounds 
               
             
          
           
               
                   
                   
                 Compound6- 
                   
                   
               
               
                 Tumor cells 
                 Cell culture 
                 93 
                 Gefitinib 
                 Taxol 
               
               
                   
               
             
          
           
               
                 Non-small-cell 
                 A549 
                 0.715 
                 33.688 
                 83.528 
               
               
                 carcinoma 
                 NCI-H1650 
                 1.366 
                 16.260 
                 0.420 
               
               
                   
                 NCI-H358 
                 0.443 
                 1.166 
                 0.278 
               
               
                 leukemia 
                 HL-60 
                 0.085 
                 34.445 
                 &lt;0.01 
               
               
                   
                 CCRF-CEM 
                 &lt;0.01 
                 12.691 
                 &lt;0.01 
               
               
                   
                 MOLT-4 
                 0.167 
                 25.839 
                 &lt;0.01 
               
               
                 Colorectal Cancer 
                 HT-29 
                 0.224 
                 18.310 
                 &gt;100 
               
               
                   
                 COLO-205 
                 0.125 
                 6.973 
                 &lt;0.01 
               
               
                 Prostate cancer 
                 DU-145 
                 0.646 
                 3.371 
                 17.428 
               
               
                   
                 PC-3 
                 1.356 
                 77.363 
                 69.019 
               
               
                 cervical cancer 
                 Hela 
                 1.509 
                 35.442 
                 &lt;0.01 
               
               
                 bladder cancer 
                 T24 
                 0.603 
                 31.346 
                 3.535 
               
               
                 nasopharyngeal 
                 CNE 
                 6.078 
                 43.682 
                 &gt;100 
               
               
                 glioma 
                 U251 
                 1.616 
                 26.801 
                 &gt;100 
               
               
                 pancreatic cancer 
                 BXPC-3 
                 0.331 
                 24.011 
                 &lt;0.01 
               
               
                 hepatocarcinoma 
                 SK-HEP-1 
                 0.489 
                 9.074 
                 0.047 
               
               
                 breast cancer 
                 MDA-MB-231 
                 0.175 
                 &gt;100 
                 2.018 
               
               
                 melanoma 
                 A375 
                 0.160 
                 35.463 
                 55.345 
               
               
                 osteosarcoma 
                 MG-63 
                 0.196 
                 33.706 
                 &lt;0.01