Abstract:
The present invention provides a compound of general formulae 3a-i to 6a-i, 7a-i to 10a-i, 12a-i to 15a-i, 16a-i to 19a-i, 21a-i to 24a-i, 25a-i to 28a-i, 30a-i to 33a-i, 34a-i to 37a-i and 39a-i to 42a-i, 43a-i to 46a-i useful as potential antitumour agents against human cancer cell lines and a process for the preparation thereof.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to Isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids as anticancer agents. Particularly, the present invention relates to Isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids of general formula A. 
         [0000]    
       
                 
         
             
             
         
       
     
       Where in G= 
       [0002]    
       
                 
         
             
             
         
       
     
         [0003]    More particularly the present invention relates to 2-[4-(5-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy Phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H quinazolin-4-one, 2-[4-(5-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one, 2-(4-(5-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxy-phenyl isoxazol-3-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one, 2-(4-(5-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxy phenyl) isoxazol-5-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one, (Z)-2-(4-(5-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3 dihydroquinazolin-4(1H)-one with aliphatic chain length variations useful as anticancer(antitumour) agents. The structural formulae of these isoxazole/isoxazoline/combretastatin-dihydroquinazolinone hybrids is given below. 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
       BACKGROUND OF THE INVENTION 
       [0004]    Inhibition of tubulin polymerization is the target of many antitumoural agents known as antimitotic agents or spindle poisons colchicines, podophyllo-toxins and combretastatins are representative examples of compounds that inhibit microtubule assembly by binding to tubulin. 2-Aryl- and 2-styrylquinazolin-4(3H)-ones(SQZ) and 2,3-dihydro-2-aryl-1-quinazolinones (DHPQ) are compounds that possess this common structural feature for an effective interaction with tubulin. The antitumor activities of 2,3-dihydro-2-aryl-4-quinazolinones (DHPQZ) were reported around 1970 (Yale H L, Kalkstein M. Substituted          nones, a new class of inhibitors of cell multiplication.  J Med Chem  1967 10, 334-336, Neil, G. L.; Li, L. H.; Buskirk, H. H.; Moxlcy, T. E.  Cancer Chemother.  1972, 56, 163-173. and Hamel, E.; Lin, C. M.; Plowman, J.; Wang, H. K.; Lee, K. H.; Paull, K. D. Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives. Interactions with tubulin.  Biochem. Pharmacol.  1996, 51, 53-59). A more recent reevaluation of this type of compound by NCl against human tumor cell lines reconfirmed that, like colchicine, they are effective inhibitors of tubulin polymerization. Many isoxazole, isoxazoline type moieties related to combretastain A-4 showed potential biological properties particularly anticancer activity (Simoni, D.; Grisolia, G.; Giannini, G.; Roberti, M.; Rondanin, R.; Piccagli, L.; Baruchello, R.; Rossi, M.; Romagnoli, R.; Invidiata, F. P.; Grimaudo, S.; Jung, M. K.; Hamel, E.; Gebbia, N.; Crosta, L.; Abbadessa, V.; DiCristina, A.; Dusonchet, L.; Meli, M.; Tolomeo, M. J. Med. Chem. 2005, 48, 723, Julia Kaffy, a Rene´e Pontikis, a, * Danie{grave over ( )}le Carrez, b Alain Croisy, Claude Monnereta and Jean-Claude Florent. Bioorg. Med. Chem. 2006, 14, 4067-4077, Gian Ceasure Tron, Tracy Pirali, Giovanni sorba, Francesca pagliai, Sara Buasacca and Armado A. Genazzani. J. Med. Chem. 2006, 49, 3033-3044. and Tracey Pirali, Sara buasacca, Lorena Beltrami, Daniela Imovilli, Francesca Paliai, Gianluca Migilio, Alberto Massrotti, Luisella Verotta, Gian Cesare Tron, Givanni Sorba, and Armado A. Genazzani. J. Med. Chem. 2006, 49, 5372-5376). Some of the heterocyclic bridged Combretastains showed an attractive profile cytotoxicity and were able to induce apoptosis at lower concentrations. 
         [0000]    
       
                 
         
             
             
         
       
     
       OBJECTIVES OF THE INVENTION 
       [0005]    The main objective of the present invention is to provide novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids useful as antitumour agents. 
         [0006]    Yet another object of this invention is to provide a process for the preparation of novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids. 
       SUMMARY OF THE INVENTION 
       [0007]    Accordingly the present invention provides a novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids of general formulae A 
         [0000]    
       
                 
         
             
             
         
       
     
       Where in G= 
       [0008]    
       
                 
         
             
             
         
       
     
         [0009]    In an embodiment of the present invention the novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids of formulae A is represented by the compounds of general formulae 3a-i to 6a-i, 7a-i to 10a-i, 12a-i to 15a-i, 16a-i to 19a-i, 21a-i to 24a-i, 25a-i to 28a-i, 30a-i to 33a-i, 34a-i to 37a-i and 39a-i to 42a-i, 43a-i to 46a-i. 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0010]    In yet another embodiment the isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids are represented by the group of the following compounds:
   2-[3-Methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3a)   2-[3-Methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3b)   2-[3-Methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3c)   2-[3-Methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3d)   2-[3-Methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3e)   2-[3-Methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3f)   2-[3-Methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3g)   2-[3-Methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3h)   2-[3-Methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3i)   6-Chloro-2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4a)   6-Chloro-2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4b)   6-Chloro-2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4c)   6-Chloro-2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4d)   6-Chloro-2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one (4e)   6-Chloro-2-[3-Methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4f)   6-Chloro-2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4g)   6-Chloro-2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4h)   6-Chloro-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(4i)   6-Methyl 2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5a)   6-Methyl 2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5b)   6-Methyl 2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5c)   6-Methyl 2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5d)   6-Methyl 2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-hexyloxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5e)   6-Methyl 2-[3-methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5f)   6-Methyl 2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5g)   6-Methyl 2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5h)   6-Methyl-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(5i)   6-Methoxy-2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6a)   6-Methoxy-2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6b)   6-Methoxy-2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6c)   6-Methoxy-2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6d)   6-Methoxy-2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6e)   6-Methoxy-2-[3-methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6f)   6-Methoxy-2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6g)   6-Methoxy-2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6h)   6-Methoxy-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(6i)   2-[4-(2-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7a)   2-[4-(3-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7b)   2-[4-(4-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7c)   2-[4-(5-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7d)   2-[4-(6-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7e)   2-[4-(7-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7f)   2-[4-(8-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7g)   2-[4-(9-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7h)   2-[4-(10-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro 1H-quinazolin-4-one(7i)   6-Chloro-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8a)   6-Chloro-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8b)   6-Chloro-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8c)   6-Chloro-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro 1H-quinazolin-4-one(8d)   6-Chloro-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8e)   6-Chloro-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8f)   6-Chloro-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8g)   6-Chloro-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8h)   6-Chloro-2-[4-(10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(8i)   6-Methyl-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9a)   6-Methyl-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9b)   6-Methyl-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9c)   6-Methyl-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9d)   6-Methyl-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9e)   6-Methyl-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9f)   6-Methyl-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9g)   6-Methyl-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9h)   6-Methyl-2-[4-(10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(9i)   6-Methoxy-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10a)   6-Methoxy-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10b)   6-Methoxy-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10c)   6-Methoxy-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10d)   6-Methoxy-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10e)   6-Methoxy-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10f)   6-Methoxy-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10g)   6-Methoxy-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10h)   6-Methoxy-2-[4-(10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(10i)   2-[3-Methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12a)   2-[3-Methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12b)   2-[3-Methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12c)   2-[3-Methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12d)   2-[3-Methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12e)   2-[3-Methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12f)   2-[3-Methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12g)   2-[3-Methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12h)   2-[3-Methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-dedyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12i)   6-Chloro-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13a)   6-Chloro-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13b)   6-Chloro-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13c)   6-Chloro-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13d)   6-Chloro-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13e)   6-Chloro-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13f)   6-Chloro-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13g)   6-Chloro-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13h)   6-Chloro-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(13i)   6-Methyl-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14a)   6-Methyl-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14b)   6-Methyl-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14c)   6-Methyl-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14d)   6-Methyl-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14e)   6-Methyl-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14f)   6-Methyl-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14g)   6-Methyl-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14h)   6-Methyl-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(14i)   6-Methoxy-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15a)   6-Methoxy-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15b)   6-Methoxy-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15c)   6-Methoxy-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15d)   6-Methoxy-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H quinazolin-4-one(15e)   6-Methoxy-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15f)   6-Methoxy-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15g)   6-Methoxy-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15h)   6-Methoxy-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(15i)   2-[4-(2-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16a)   2-[4-(3-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16b)   2-[4-(4-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16c)   2-[4-(5-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16d)   2-[4-(6-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16e)   2-[4-(7-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16f)   2-[4-(8-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16g)   2-[4-(9-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16h)   2-[4-(10-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16i)   6-Chloro-2-[4-(2-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(17a)   6-Chloro-2-[4-(3-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(17b)   6-Chloro-2-[4-{4-(2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(17c)   6-Chloro-2-[4-(5-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17d)   6-Chloro-2-[4-(6-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17e)   6-Chloro-2-[4-(7-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17f)   6-Chloro-2-[4-(8-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17g)   6-Chloro-2-[4-(9-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17h)   6-Chloro-2-[4-(10-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(17i)   6-Methyl-2-[4-(2-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(18a)   6-Methyl-2-[4-(3-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(18b)   6-Methyl-2-[4-(4-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(18c)   6-Methyl-2-[4-(5-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18d)   6-Methyl-2-[4-(6-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-Methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18e)   6-Methyl-2-[4-(7-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18f)   6-Methyl-2-[4-(8-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18g)   6-Methyl-2-[4-(9-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18h)   6-Methyl-2-[4-(10-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(18i)   6-Methoxy-2-[4-(2-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(19a)   6-Methoxy-2-[4-(3-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(19b)   6-Methoxy-2-[4-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]=phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(19c)   6-Methoxy-2-[4-(5-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19d)   6-Methoxy-2-[4-(6-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19e)   6-Methoxy-2-[4-(7-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19f)   6-Methoxy-2-[4-(8-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19g)   6-Methoxy-2-[4-(9-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19h)   6-Methoxy-2-[4-(10-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]2,3-dihydro-1H-quinazolin-4-one(19i)   2-(3-methoxy-4-(2-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)ethoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21a)   2-(3-methoxy-4-(3-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)propoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21b)   2-(3-methoxy-4-(4-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl) isoxazol-3-yl)phenoxy)butoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21c)   2-(3-methoxy-4-(5-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21d)   2-(3-methoxy-4-(6-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl) isoxazol-3-yl)phenoxy)hexyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21e)   2-(3-methoxy-4-(7-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)heptyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21f)   2-(3-methoxy-4-(8-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)octyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21g)   2-(3-methoxy-4-(9-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)nonyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21h)   2-(3-methoxy-4-(10-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)decyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21i)   6-Chloro-2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22a)   6-Chloro-2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22b)   6-Chloro-2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22c)   6-Chloro-2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22d)   6-Chloro-2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22e)   6-Chloro-2-[3-methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22f)   6-Chloro-2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22g)   6-Chloro-2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22h)   6-Chloro-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(22i)   6-Methyl-2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23a)   6-Methyl-2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23b)   6-Methyl-2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23c)   6-Methyl-2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23d)   6-Methyl-2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23e)   6-Methyl-2-[3-methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23f)   6-Methyl-2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23g)   6-Methyl-2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23h)   6-Methyl-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(23i)   6-Methoxy-2-[3-methoxy-4-(2-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24a)   6-Methoxy-2-[3-methoxy-4-(3-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24b)   6-Methoxy-2-[3-methoxy-4-(4-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24c)   6-Methoxy-2-[3-methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24d)   6-Methoxy-2-[3-methoxy-4-(6-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24e)   6-Methoxy-2-[3-methoxy-4-(7-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24f)   6-Methoxy-2-[3-methoxy-4-(8-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24g)   6-Methoxy-2-[3-methoxy-4-(9-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24h)   6-Methoxy-2-[3-methoxy-4-(10-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(24i)   2-(4-(2-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)ethoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25a)   2-(4-(3-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)propoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25b)   2-(4-(4-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)butoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25c)   2-(4-(5-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25d)   2-(4-(6-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)hexyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25e)   2-(4-(7-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)heptyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25f)   2-(4-(8-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)octyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25g)   2-(4-(7-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)heptyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25h)   2-(4-(8-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)octyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25i)   2-(4-(9-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)nonyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25h)   2-(4-(10-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)decyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(25i)   6-Chloro-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26a)   6-Chloro-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26b)   6-Chloro-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26c)   6-Chloro-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26d)   6-Chloro-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26e)   6-Chloro-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26f)   6-Chloro-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26g)   6-Chloro-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26h)   6-Chloro-2-[4-10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(26i)   6-Methyl-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27a)   6-Methyl-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27b)   6-Methyl-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27c)   6-Methyl-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27d)   6-Methyl-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27e)   6-Methyl-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27f)   6-Methyl-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27g)   6-Methyl-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27h)   6-Methyl-2-[4-(10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(27i)   6-Methoxy-2-[4-(2-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28a)   6-Methoxy-2-[4-(3-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28b)   6-Methoxy-2-[4-(4-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28c)   6-Methoxy-2-[4-(5-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28d)   6-Methoxy-2-[4-(6-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28e)   6-Methoxy-2-[4-(7-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28f)   6-Methoxy-2-[4-(8-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28g)   6-Methoxy-2-[4-(9-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28h)   6-Methoxy-2-[4-(10-{2,6-dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-isoxazol-3-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(28i)   2-(3-methoxy-4-(2-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)ethoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30a)   2-(3-methoxy-4-(3-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)propoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30b)   2-(3-methoxy-4-(4-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)butoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30c)   2-(3-methoxy-4-(5-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30d)   2-(3-methoxy-4-(6-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)hexyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30e)   2-(3-methoxy-4-(7-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)heptyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30f)   2-(3-methoxy-4-(8-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)octyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30g)   2-(3-methoxy-4-(9-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)nonyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30h)   2-(3-methoxy-4-(10-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)decyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30i)   6-Chloro-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31a)   6-Chloro-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31b)   6-Chloro-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31c)   6-Chloro-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31d)   6-Chloro-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31e)   6-Chloro-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31f)   6-Chloro-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31g)   6-Chloro-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31h)   6-Chloro-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(31i)   6-Methyl-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32a)   6-Methyl-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32b)   6-Methyl-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32c)   6-Methyl-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32d)   6-Methyl-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32e)   6-Methyl-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32f)   6-Methyl-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32g)   6-Methyl-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32h)   6-Methyl-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(32i)   6-Methoxy-2-[3-methoxy-4-(2-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33a)   6-Methoxy-2-[3-methoxy-4-(3-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33b)   6-Methoxy-2-[3-methoxy-4-(4-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33c)   6-Methoxy-2-[3-methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33d)   6-Methoxy-2-[3-methoxy-4-(6-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33e)   6-Methoxy-2-[3-methoxy-4-(7-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33f)   6-Methoxy-2-[3-methoxy-4-(8-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33g)   6-Methoxy-2-[3-methoxy-4-(9-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33h)   6-Methoxy-2-[3-methoxy-4-(10-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(33i)   2-(4-(2-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)ethoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34a)   2-(4-(3-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)propoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34b)   2-(4-(4-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)butoxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34c)   2-(4-(5-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34d)   2-(4-(6-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)hexyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34e)   2-(4-(7-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)heptyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34f)   2-(4-(8-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)octyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34g)   2-(4-(9-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl(isoxazol-5-yl)phenoxy)nonyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34h)   2-(4-(10-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)decyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34i)   6-Chloro-2-[4-(2-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35a)   6-Chloro-2-[4-(3-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35b)   6-Chloro-2-[4-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35c)   6-Chloro-2-[4-(5-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35d)   6-Chloro-2-[4-(6-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35e)   6-Chloro-2-[4-(7-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35f)   6-Chloro-2-[4-(8-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35g)   6-Chloro-2-[4-(9-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35h)   6-Chloro-2-[10-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(35i)   6-Methyl-2-[4-(2-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36a)   6-Methyl-2-[4-(3-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36b)   6-Methyl-2-[4-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36c)   6-Methyl-2-[4-(5-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36d)   6-Methyl-2-[4-(6-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36e)   6-Methyl-2-[4-(7-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36f)   6-Methyl-2-[4-(8-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36g)   6-Methyl-2-[4-(9-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36h)   6-Methyl-2-[10-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(36i)   6-Methoxy-2-[4-(2-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37a)   6-Methoxy-2-[4-(3-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37b)   6-Methoxy-2-[4-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-butyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37c)   6-Methoxy-2-[4-(5-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37d)   6-Methoxy-2-[4-(6-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37e)   6-Methoxy-2-[4-(7-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37f)   6-Methoxy-2-[4-(8-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37g)   6-Methoxy-2-[4-(9-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37h)   6-Methoxy-2-[10-(4-{2,6-dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-isoxazol-5-yl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(37i)   (Z)-2-(3-methoxy-4-(2-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)ethoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39a)   (Z)-2-(3-methoxy-4-(3-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)propoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39b)   (Z)-2-(3-methoxy-4-(4-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)butoxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39c)   (Z)-2-(3-methoxy-4-(5-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39d)   (Z)-2-(3-methoxy-4-(6-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)hexyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39e)   (Z)-2-(3-methoxy-4-(7-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)heptyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39f)   (Z)-2-(3-methoxy-4-(8-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)octyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39g)   (Z)-2-(3-methoxy-4-(9-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)nonyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39h)   (Z)-2-(3-methoxy-4-(10-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)decyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39i)   6-Chloro-2-[3-methoxy-4-(2-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40a)   6-Chloro-2-[3-Methoxy-4-(3-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40b)   6-Chloro-2-[3-Methoxy-4-(4-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40c)   6-Chloro-2-[3-methoxy-4-(5-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40d)   6-Chloro-2-[3-Methoxy-4-(6-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40e)   6-Chloro-2-[3-Methoxy-4-(7-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40f)   6-Chloro-2-[3-methoxy-4-(8-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40g)   6-Chloro-2-[3-Methoxy-4-(9-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40h)   6-Chloro-2-[3-Methoxy-4-(10-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(40i)   6-Methyl-2-[3-methoxy-4-(2-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41a)   6-Methyl-2-[3-Methoxy-4-(3-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41b)   6-Methyl-2-[3-Methoxy-4-(4-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41c)   6-Methyl-2-[3-methoxy-4-(5-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41d)   6-Methyl-2-[3-Methoxy-4-(6-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41e)   6-Methyl-2-[3-Methoxy-4-(7-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41f)   6-Methyl-2-[3-methoxy-4-(8-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41g)   6-Methyl-2-[3-Methoxy-4-(9-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41h)   6-Methyl-2-[3-Methoxy-4-(10-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(41i)   6-Methoxy-2-[3-methoxy-4-(2-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42a)   6-Methoxy-2-[3-Methoxy-4-(3-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl-]phenoxy}-propoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42b)   6-Methoxy-2-[3-Methoxy-4-(4-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42c)   6-Methoxy-2-[3-methoxy-4-(5-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42d)   6-Methoxy-2-[3-Methoxy-4-(6-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42e)   6-Methoxy-2-[3-Methoxy-4-(7-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42f)   6-Methoxy-2-[3-methoxy-4-(8-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl-]phenoxy}-octyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42g)   6-Methoxy-2-[3-Methoxy-4-(9-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42h)   6-Methoxy-2-[3-Methoxy-4-(10-{2-methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(42i)   (Z)-2-(4-(2-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)ethoxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43a)   (Z)-2-(4-(3-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)propoxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43b)   (Z)-2-(4-(4-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)butoxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43c)   (Z)-2-(4-(5-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)pentyoxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43d)   (Z)-2-(4-(6-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)hexyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43e)   (Z)-2-(4-(7-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)heptyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43f)   (Z)-2-(4-(8-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)octyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43g)   (Z)-2-(4-(9-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)nonyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43h)   (Z)-2-(4-(10-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)decyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43i)   6-Chloro-2-[4-(2-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44a)   6-Chloro-2-[4-(3-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44b)   6-Chloro-2-[4-(4-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44c)   6-Chloro-2-[4-(5-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44d)   6-Chloro-2-[4-(6-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44e)   6-Chloro-2-[4-(7-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44f)   6-Chloro-2-[4-(8-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (44g)   6-Chloro-2-[4-(9-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44h)   6-Chloro-2-[4-(10-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(44i)   6-Methyl-2-[4-(2-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45a)   6-Methyl-2-[4-(3-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-Phenyl)-vinyl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45b)   6-Methyl-2-[4-(4-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (45c)   6-Methyl-2-[4-(5-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45d)   6-Methyl-2-[4-(6-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45e)   6-Methyl-2-[4-(7-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45f)   6-Methyl-2-[4-(8-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45g)   6-Methyl-2-[4-(9-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45h)   6-Methyl-2-[4-(10-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(45i)   6-Methoxy-2-[4-(2-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-ethoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46a)   6-Methoxy-2-[4-(3-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-propoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46b)   6-Methoxy-2-[4-(4-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-butoxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46c)   6-Methoxy-2-[4-(5-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46d)   6-Methoxy-2-[4-(6-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-hexyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46e)   6-Methoxy-2-[4-(7-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-heptyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46f)   6-Methoxy-2-[4-(8-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-octyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46g)   6-Methoxy-2-[4-(9-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-nonyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46h)   6-Methoxy-2-[4-(10-{2,6-dimethoxy-4-[2-(3,4,5-trimethoxy-phenyl)-vinyl]-phenoxy}-decyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(46i)   
 
         [0373]    The present invention further provides a process for preparation of novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids of general formulae 3a-i to 6a-i, 7a-i to 10a-i, 12a-i to 15a-i, 16a-i to 19a-i, 21a-i to 24a-i, 25a-i to 28a-i, 30a-i to 33a-i, 34a-i to 37a-i and 39a-i to 42a-i, 43a-i to 46a-i which comprises 
         [0000]    Reacting 2-[4-(n-Bromo-alkyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one of formula 2 with the compounds of formulae 1a, 1b, 11a, 11b, 20a, 20b, 29a, 29b, 38a, 38b respectively in an aprotic water miscible organic solvent, in the presence of anhydrous mild inorganic base, under room temperature for a period of about 48 hrs, followed by the removal of inorganic base by filtration and evaporating the organic solvent to obtain the resultant crude product and purifying it by column chromatography to obtain the desired products of formulae 3a-i to 6a-i, 7a-i to 10a-i, 12a-i to 15a-i, 16a-i to 19a-i, 21a-i to 24a-i, 25a-i to 28a-i, 30a-i to 33a-i, 34a-i to 37a-i and 39a-i to 42a-i, 43a-i to 46a-i respectively. 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0374]    The precursor dihydroquinazolinone of formula 2, has been prepared using literature method (Mann-Jen Hour, † Li-Jiau Huang, † Sheng-Chu Kuo, *, † Yi Xia, ‡ Kenneth Bastow, §Yuka Nakanishi, §Ernest Hamel, | and Kuo-Hsiung Lee*, ‡  J. Med. Chem.  2000, 43, 4479-4487). The precursors isoxazoles, isoxazolines and combretastatins of formulae 1(a&amp;b), 11(a&amp;b), 20(a&amp;b), 29(a&amp;b) and 38(a&amp;b) have been prepared using literature methods (Julia kaffy, Renee Pontikis, Daniele Carrez, Alain Croisy, Claude Monneret and Jean-Claude Florent. Bioorg. Med. Chem. 2006, 14, 4067-4077, Simoni, D.; Grisolia, G.; Giannini, G.; Roberti, M.; Rondanin, R.; Piccagli, L.; Baruchello, R.; Rossi, M.; Romagnoli; R.; Invidiata, F. P.; Grimaudo, S.; Jung, M. K.; Hamel, E.; Gebbia, N.; Crosta, L.; Abbadessa, V.; DiCristina, A.; Dusonchet, L.; Meli, M.; Tolomeo, M. J. Med. Chem. 2005, 48, 723) 
         [0375]    These new analogues of isoxazole/isoxazoline/combretastatin linked dihydro-quinazolinone hybrids have shown promising anticancer activity in various cell lines. The molecules synthesized are of immense biological significance. This resulted in design and synthesis of new congener&#39;s as illustrated in schemes 1-5 which comprise: 
         [0376]    The ether linkage between dihydroquinazolinone of formula 2 and isoxazole/isoxazoline/combretastatins of formulae 1(a&amp;b), 11(a&amp;b), 20(a&amp;b), 29(a&amp;b) and 38(a&amp;b)
       1. Stirring the reaction mixtures at a temperature of 35° C. for 30 h.   2. Synthesis of isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids.   3. Purification by column chromatography using different solvents like ethyl acetate, hexane, dichloromethane and methanol.       
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0380]    The following examples are given by way of illustration and therefore should not be construed to the present limit of the scope of invention. 
       Example 1 
     2-[3-Methoxy-4-(5-{2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(3d) 
       [0381]    2-Methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenol(1a) (359.37 mg, 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.31 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (3d) (557 mg, 80% yield). 
         [0382]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.69-3.82 (dd, 1H, J=10.7 Hz, J=16.4 Hz), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s; 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 5.63-5.73 (t, 1H, J=10.1 Hz, J=9.2 Hz), 5.77 (s, 1H), 6.57-6.61 (d, 1H, J=7.9 Hz), 6.63 (s, 1H) 6.76-6.79 (d, 1H, J=8.1 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.87 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 698.75 (M+H) − . 
       Example 2 
     2-[4-(5-{2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenoxy}pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(7d)2,6-Dimethoxy-4-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-3-yl]-phenol (1b) 
       [0383]    (389.15 mg, 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.31 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (7d) (583 mg, 80% yield). 
         [0384]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.69-3.82 (dd, 1H, J=10.7 Hz, J=16.4 Hz), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 5.63-5.73 (t, 1H, J=10.1 Hz, J=9.2 Hz), 5.77 (s, 1H), 6.62 (s, 2H), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 728.78M+H) + . 
       Example 3 
     2-[3-Methoxy-4-(5-{2-methoxy-5-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-phenyl]-2,3-dihydro-1H-quinazolin-4-one(12d) 
       [0385]    2-Methoxy-5-[3-(3,4,5-trimethoxy-Phenyl)-4,5-dihydro-isoxazol-5-yl]phenol(11a) (359.37 mg, 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.31 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (12d) (546 mg, 80% yield). 
         [0386]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.69-3.82 (dd, 1H, J=10.7 Hz, J=16.4 Hz), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 5.63-5.73 (t, 11-1, J=10.1 Hz, J=9.2 Hz), 5.77 (s, 1H), 6.57-6.61 (d, 1H, J=7.9 Hz), 6.63 (s, 1H) 6.76-6.79 (d, 1H, J=8.1 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2Hz), 7.82-7.87 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 698.75 (M+H) + . 
       Example 4 
     2-[4-(5-{2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenoxy}-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(16d) 
       [0387]    2,6-Dimethoxy-4-[3-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-phenol (11b)(389.40 mg, 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.31 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (16d) (570 mg, 80% yield). 
         [0388]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.69-3.82 (dd, 1H, J=10.7 Hz, J=16.4 Hz), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 5.63-5.73 (t, 1H, J=10.1 Hz, J=9.2 Hz), 5.77 (s, 1H), 6.62 (s, 2H), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 728.80 (M+H) + . 
       Example 5 
     2-(3-methoxy-4-(5-(2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(21d) 
       [0389]    2-methoxy-5-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenol (20a) (357.36 mg 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (21d) (546 mg, 80% yield). 
         [0390]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.57-6.61 (d, 1H, J=7.9 Hz), 6.63 (s, 1H), 6.67 (s, 1H), 6.76-6.79 (d, 1H, J=8.1 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.87 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 696.76 (M+H) + . 
       Example 6 
     2-(4-(5-(2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (25d) 
       [0391]    2,6-dimethoxy-4-(5-(3,4,5-trimethoxyphenyl)isoxazol-3-yl)phenol (20b) (387.38 mg, 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (25d) (546 mg, 80% yield). 
         [0392]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.62 (s, 2H), 6.67 (s, 1H) 6.82-6.85 (d, 1H, J=7.7 Hz), 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 726.78 (M+H) + . 
       Example 7 
     2-(3-methoxy-4-(5-(2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(30d) 
       [0393]    2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenol (290 (357.36 mg 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (30d) (546 mg, 80% yield). 
         [0394]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.57-6.61 (d, 1H, J=7.9 Hz), 6.63 (s, 1H), 6.67 (s, 1H), 6.76-6.79 (d, 1H, J=8.1 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz) 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.87 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 696.76 (M+H) + . 
       Example 8 
     2-(4-(5-(2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenoxy)pentyloxy)-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one(34d) 
       [0395]    2,6-dimethoxy-4-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenol (29b) (387.38 mg 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one (2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (34d) (546 mg, 80% yield). 
         [0396]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.62 (s, 2H), 6.67 (s, 1H) 6.82-6.85 (d, 1H, J=7.7 Hz), 6.88 (s, 2H), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.74 Hz J=7.55 Hz) FABMS: 726.78 (M+H) + . 
       Example 9 
     (Z)-2-(3-methoxy-4-(5-(2-methoxy-5-(3,4,5-trimethoxystyryl)phenoxy)pentyloxy)phenyl)-2,3-dihydroquinazolin-4(1H)-one(39d) 
       [0397]    (Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenol (38a) (316.35 mg 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (39d) (546 mg, 80% yield). 
         [0398]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.2 Hz), 4.10-4.16 (t, 2H, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.39 (d, 2H, J=4.4 Hz), 6.47 (s, 2H) 6.73 (d, 1H, 2.2 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz), 6.89 (d, 1H, J=2.2 Hz), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.55 Hz J=7.74 Hz) FABMS: 655.75M+H) + . 
       Example 10 
     (Z)-2-(4-(5-(2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenoxy)pentyloxy)-3-methoxy phenyl)-2,3-dihydroquinazolin-4(1H)-one(43d) 
       [0399]    (Z)-2,6-dimethoxy-4-(3,4,5-trimethoxystyryl)phenol (38b) (346.37.36 mg 1.0 mmol) in DMF (20 mL) was added anhydrous potassium carbonate (690 mg, 5.0 mmol) and 2-[4-(5-Bromo-pentyloxy)-3-methoxy-phenyl]-2,3-dihydro-1H-quinazolin-4-one(2d) (419.29 mg, 1.0 mmol). The reaction mixture was stirred at a temperature of 30° C. for 30 h and the reaction was monitored by TLC using ethyl acetate-hexane (6:4) as a solvent system. Then to this ice is added and extracted with ethyl acetate. The solvent was evaporated under vacuum to afford the crude product. This was further purified by column chromatography using ethyl acetate:hexane (6:4) as a solvent system to obtain the pure product (43d) (546 mg, 80% yield). 
         [0400]      1 H NMR (CDCl 3 ): δ 1.70-1.80 (m, 2H), 1.89-2.02 (m, 4H), 3.84 (s, 6H), 3.87 (s, 3H), 3.92 (s, 3H), 3.89 (s, 6H), 3.94 (s, 3H), 4.02-4.08 (t, 2H, J=5.2 Hz), 4.10-4.16 (t, 21-1, J=6.4 Hz), 4.39-4.42 (bs, NH), 6.04 (s, 1H), 6.47 (s, 2H), 6.70 (s, 2H), 6.73 (d, 1H, J=2.2 Hz), 6.82-6.85 (d, 1H, J=7.7 Hz), 6.89 (d, 11-1, J=2.2 Hz), 6.90 (s, 1H), 6.94-6.97 (d, 1H, J=7.7 Hz), 7.18-7.21 (m, 2H), 7.22-7.29 (dd, 1H, J=7.5 Hz J=15.2 Hz), 7.82-7.92 (dd, 1H, J=7.55 Hz J=7.74 Hz): FABMS: 685.77M+H) + . 
       Biological Activity: 
       [0401]    some of in vitro biological activity studies were carried out at the National Cancer Institute, Maryland, USA. 
       In Vitro Cytotoxicity 
       [0402]    The isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrid (7d) has been tested against forty nine human tumour cell lines derived from nine cancer types (leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) as per NCI protocol. For each compound, dose response curves for individual cell lines have been measured at a minimum of five concentrations at 10 fold dilutions. A protocol of 48 h continuous drug exposure has been used, and a sulforhodamine B (SRB) protein assay was used to estimate cell viability or growth. The concentration for 50% cell growth inhibition (GI 50 ), total cell growth inhibition (TGI, 0% growth) and 50% cell death (LC 50 , 50% growth) compared with the control has been calculated (Table-1). Compound 7d has been evaluated for their in vitro cytotoxicity in forty nine cell lines from nine human cancer types of lung (Hop-62, NCI-H226, NCI-H522), leukemia (K-562, SR), colon (HCT-116, HCT-15, HCC-2998), CNS(SF-539), melanoma (SK-MEL-5, MDA-MB-435, UACC-62, M14), ovarian (IGROV1), renal (A498), prostate (PC3) breast (BT-549, HS578T)origin. The results are expressed as percent of cell growth determined relative to that of untreated control cells (Table 2). The representative compound 7d has shown significant cytotoxicity against some cancer cell lines. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Log 10  GI 50  (concentration in mol/L causing 50% growth 
               
               
                 inhibition) values for quinazolinone-PBD hybrid(7d) 
               
             
          
           
               
                   
                 Log 10  GI50 
                 Log 10  LC50 
               
               
                   
                   
               
             
          
           
               
                   
                 Leukemia 
                 −6.17 
                 −4.15 
               
               
                   
                 Non-small-celllung 
                 −4.97 
                 −4.00 
               
               
                   
                 Colon 
                 −5.17 
                 −4.00 
               
               
                   
                 CNS 
                 −4.66 
                 −4.00 
               
               
                   
                 Melanoma 
                 −5.69 
                 −4.00 
               
               
                   
                 Ovarian 
                 −5.20 
                 −4.00 
               
               
                   
                 Renal 
                 −4.72 
                 −4.00 
               
               
                   
                 Prostate 
                 −5.39 
                 −4.00 
               
               
                   
                 Breast 
                 −5.82 
                 −4.00 
               
               
                   
                   
               
               
                   
                 Each cancer type represents the average of six to eight different cancer cell lines. 
               
             
          
         
       
     
         [0403]    The compound 7d exhibits a wide spectrum of activity against forty nine cell lines in nine cell panels, with GI 50  value of &lt;40 μm. In the non-small cell lung cancer panel, the growth of EKVX, NCI-H3 cell lines were affected by compound 7d with GI 50  values as 0.36 and 0.38 μM respectively. The GI 50  values of compound 7d against colon cancer HCC-2998, FICT-116 cell lines are 0.06 and 0.26 μm respectively. The GI 50  values for compound 7d against leukemia CCRF-CEM, K-562, MOLT-4 and RPMI-8226 cell lines are 0.62, 0.37, 0.68 and 0.06 μm respectively. The GI 50  values for compound 7d against melanoma SK-MEL-5, UACC-257, MDA-MB-435, and UACC-62 cell lines are 0.18, 0.29, 0.60 and 0.99 μm respectively. The GI 50  values for compound 7d against ovarian IGROV1 and OVCAR-4 cell lines are 0.32 and 0.49 μM. The GI 50  values for compound 7d against renal ACHN cell line is 0.95 μm The GI 50  values for compound 7d against prostate PC-3 cell line is 0.74 μm. The GI 50  values for compound 7d against breast MCF7, T-47D. MDA-MB-468 cell lines are 0.45, 0.30, 0.08 μm respectively. 
         [0404]    Compound 7d exhibits activity against forty nine cell lines in nine cancer cell panels with GI 50  values of &lt;40 μm. in vitro cytotoxicity of compound 7d in selected cancer cell lines has been illustrated in Table 2. The average GI 50  values for each cancer panel of compounds 7d have been illustrated in Tablet. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 In vitro cytotoxicity of compounds 7d in 
               
               
                 forty nine cancer cell lines 
               
             
          
           
               
                   
                 Cancer panel/ 
                 GI 50   
               
               
                   
                 cell line 
                 (μm) 7d 
               
               
                   
                   
               
             
          
           
               
                   
                 Leukemia 
                   
               
               
                   
                 CCRF-CEM 
                 0.62 
               
               
                   
                 HL-60(TB) 
                 12.2 
               
               
                   
                 K-562 
                 0.37 
               
               
                   
                 MOLT-4 
                 0.68 
               
               
                   
                 RPMI-8226 
                 0.06 
               
               
                   
                 Non-small 
               
               
                   
                 cell lung 
               
               
                   
                 A549/ATCC 
                 15.7 
               
               
                   
                 EKVX 
                 0.36 
               
               
                   
                 HOP-92 
                 15.8 
               
               
                   
                 NCI-H23 
                 0.38 
               
               
                   
                 NCI-H460 
                 15.1 
               
               
                   
                 NCI-H522 
                 27.4 
               
               
                   
                 Colon 
               
               
                   
                 HCC-2998 
                 0.06 
               
               
                   
                 HCT-116 
                 0.26 
               
               
                   
                 HCT-15 
                 15.9 
               
               
                   
                 KM12 
                 10.4 
               
               
                   
                 SW-620 
                 21.0 
               
               
                   
                 CNS 
               
               
                   
                 SF-268 
                 20.2 
               
               
                   
                 SF-295 
                 16.4 
               
               
                   
                 SF-539 
                 21.2 
               
               
                   
                 SNB-19 
                 16.6 
               
               
                   
                 SNB-75 
                 34.2 
               
               
                   
                 U251 
                 25.2 
               
               
                   
                 Melanoma 
               
               
                   
                 LOX IMVI 
                 19.5 
               
               
                   
                 M14 
                 19.8 
               
               
                   
                 Ovarian 
               
               
                   
                 IGROV1 
                 0.32 
               
               
                   
                 OVCAR-3 
                 12.4 
               
               
                   
                 OVCAR-4 
                 0.49 
               
               
                   
                 OVCAR-5 
                 31.7 
               
               
                   
                 OVCAR-8 
                 25.7 
               
               
                   
                 SK-OV-3 
                 38.5 
               
               
                   
                 NCI/ADRRES 
                 10.6 
               
               
                   
                 Renal 
               
               
                   
                 786-0 
                 31.8 
               
               
                   
                 A498 
                 19.3 
               
               
                   
                 ACHN 
                 0.95 
               
               
                   
                 CAKI-1 
                 18.0 
               
               
                   
                 SN12C 
                 39.1 
               
               
                   
                 UO-31 
                 21.4 
               
               
                   
                 Prostate 
               
               
                   
                 PC-3 
                 0.74 
               
               
                   
                 DU-145 
                 22.4 
               
               
                   
                 Breast 
               
               
                   
                 MCF7 
                 0.45 
               
               
                   
                 MDA-MB-231/ATCC 
                 14.7 
               
               
                   
                 HS 578T 
                 15.0 
               
               
                   
                 T-47D 
                 0.30 
               
               
                   
                 MDA-MB-468 
                 0.08 
               
               
                   
                 Melanoma 
               
               
                   
                 SK-MEL-28 
                 3.24 
               
               
                   
                 SK-MEL-5 
                 0.18 
               
               
                   
                 UACC-257 
                 0.29 
               
               
                   
                 UACC-62 
                 0.99 
               
               
                   
                 MDA-MB-435 
                 0.60 
               
               
                   
                   
               
             
          
         
       
     
         [0405]    The mean graph mid point values of log 10  TGI and log 10  LC 50  as well as log 10  GI 50  for 7d is listed in Table-3. As demonstrated by mean graph pattern, compounds 7d exhibit an interesting profile of activity and selectivity for various cell lines. The mean graph mid points of log 10  TGI and log 10  LC 50  have shown similar pattern to the log 10  GI 50  mean graph mid points. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 log 10  GI 50 , log 10  TGI and log 10  LC 50  mean graphs midpoints 
               
               
                 (MG_MID) of in vitro cytotoxicity data for the compound 
               
               
                 7d.against human tumour cell lines. 
               
             
          
           
               
                   
                 Compound 
                 Log 10  GI 50   
                 Log 10  TGI 
                 Log 10  LC 50   
               
               
                   
                   
               
               
                   
                 7d 
                 −5.28 
                 −4.18 
                 −4.02 
               
               
                   
                   
               
             
          
         
       
     
       Significance of the Work Carried Out 
       [0406]    The novel dihydroquinazolinone-isoxazole/isoxazoline/combretastatin hybrids that have been synthesized exhibited significant cytotoxic activity against forty nine human tumour cell lines. 
       ADVANTAGES OF THE INVENTION 
       [0000]    
       
         
           
             1. The present invention provides a new dihydroquinazolinone-isoxazole/isoxazoline/combretastatin hybrids useful as antitumour agents. 
             2. It also provides a process for the preparation of novel dihydroquinazolinone-isoxazole/isoxazoline/combretastatin hybrids.