Isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids as potential anticancer agents and process for the preparation thereof

Description

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Stage application under 35 U.S.C. §371 of International Patent Application Serial No. PCT/IN2009/000490, filed Sep. 8, 2009, which claims the benefit of the Indian Patent Application No. 2602/DEL/2008, filed Nov. 19, 2008, the disclosures of each of which are expressly incorporated by reference in their entireties.

FIELD OF THE INVENTION

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.

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Where in G=

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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.

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BACKGROUND OF THE INVENTION

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-4-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 2,3-dihydro-4(1H)-quinazolinones, 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 NCI 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 Renée Pontikis,a,* Danièle 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.

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OBJECTIVES OF THE INVENTION

The main objective of the present invention is to provide novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids useful as antitumour agents.

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

Accordingly the present invention provides a novel isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids of general formulae A

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Where in G=

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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.

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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)-4,5 dihydro-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)

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

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.

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DETAILED DESCRIPTION OF THE INVENTION

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&b), 11(a&b), 20(a&b), 29(a&b) and 38(a&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)

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's as illustrated in schemes 1-5 which comprise:

The ether linkage between dihydroquinazolinone of formula 2 and isoxazole/isoxazoline/combretastatins of formulae 1(a&b), 11(a&b), 20(a&b), 29(a&b) and 38(a&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.

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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)

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).

¹H NMR (CDCl₃): 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)

(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).

¹H NMR (CDCl₃): 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)

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).

¹H NMR (CDCl₃): 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=15.2Hz), 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)

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).

¹H NMR (CDCl₃): 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)

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).

¹H NMR (CDCl₃): 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)

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).

¹H NMR (CDCl₃): 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)

2-methoxy-5-(3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)phenol (29a) (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).

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)

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).

¹H NMR (CDCl₃): 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)

(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).

¹H NMR (CDCl₃): 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)

(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).

¹H NMR (CDCl₃): 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

some of in vitro biological activity studies were carried out at the National Cancer Institute, Maryland, USA.

In Vitro Cytotoxicity

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 (GI₅₀), total cell growth inhibition (TGI, 0% growth) and 50% cell death (LC₅₀, 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.

TABLE 1

Log₁₀GI₅₀(concentration in mol/L causing 50% growth

inhibition) values for quinazolinone-PBD hybrid(7d)

Log₁₀GI50
Log₁₀LC50

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.

The compound 7d exhibits a wide spectrum of activity against forty nine cell lines in nine cell panels, with GI₅₀value of <40 μm. In the non-small cell lung cancer panel, the growth of EKVX, NCI-H3 cell lines were affected by compound 7d with GI₅₀values as 0.36 and 0.38 μM respectively. The GI₅₀values of compound 7d against colon cancer HCC-2998, HCT-116 cell lines are 0.06 and 0.26 μm respectively. The GI₅₀values 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 GI₅₀values 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 GI₅₀values for compound 7d against ovarian IGROV1 and OVCAR-4 cell lines are 0.32 and 0.49 μM. The GI₅₀values for compound 7d against renal ACHN cell line is 0.95 μm The GI₅₀values for compound 7d against prostate PC-3 cell line is 0.74 μm. The GI₅₀values for compound 7d against breast MCF7, T-47D. MDA-MB-468 cell lines are 0.45, 0.30, 0.08 μm respectively.

Compound 7d exhibits activity against forty nine cell lines in nine cancer cell panels with GI₅₀values of <40 μm. in vitro cytotoxicity of compound 7d in selected cancer cell lines has been illustrated in Table 2. The average GI₅₀values for each cancer panel of compounds 7d have been illustrated in Tablet.

TABLE 2

In vitro cytotoxicity of compounds 7d in

forty nine cancer cell lines

Cancer panel/
GI₅₀

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

The mean graph mid point values of log₁₀TGI and log₁₀LC₅₀as well as log₁₀GI₅₀for 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 log₁₀TGI and log₁₀LC₅₀have shown similar pattern to the log₁₀GI₅₀mean graph mid points.

TABLE 3

log₁₀GI₅₀, log₁₀TGI and log₁₀LC₅₀mean graphs midpoints

(MG_MID) of in vitro cytotoxicity data for the compound

7d.against human tumour cell lines.

Compound
Log₁₀GI₅₀
Log₁₀TGI
Log₁₀LC₅₀

7d
−5.28
−4.18
−4.02

Significance of the Work Carried Out

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

- 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.

Claims

1. An isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound of general formulae A
2. The isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound as claimed in claim 1 wherein the isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound of formula A wherein the compound is represented by general formulae 3a-i to 6a-1, 7a-i to 10a-1, 12a-i to 15a-1, 16a-i to 19a-1, 21a-i to 24a-1, 25a-i to 28a-1, 30a-i to 33a-1, 3-a-i to 37a-i and 39a-i to 42a-1, 43a-i to 46a-i
3. The isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound as claimed in claim 1 wherein the compound is 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)-4,5 dihydro-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-(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); or6-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).
4. The isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound as claimed in claim 1 wherein the compound is:
5. A process for the preparation of a isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone compound of general formulae A
6. The process as claimed in claim 5, wherein the aprotic water miscible organic solvent is selected from the group consisting of dimethylformamide, acetone, acetonitrile and dimethyl sulfoxide.
7. The process as claimed in claim 5, wherein the anhydrous mild inorganic base is selected from the group consisting of sodium carbonate or potassium carbonate.
8. A pharmaceutical composition comprising a compound of formula A according to claim 1 and a pharmaceutically acceptable carrier.

Priority Claims (1)

Number	Date	Country	Kind
2602/DEL/2008	Nov 2008	IN	national

PCT Information

Filing Document	Filing Date	Country	Kind	371c Date
PCT/IN2009/000490	9/8/2009	WO	00	1/2/2012

Publishing Document	Publishing Date	Country	Kind
WO2010/058417	5/27/2010	WO	A

Foreign Referenced Citations (1)

Number	Date	Country
WO-9520567	Aug 1995	WO

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Related Publications (1)

	Number	Date	Country
	20120283439 A1	Nov 2012	US

Isoxazole/isoxazoline/combretastatin linked dihydroquinazolinone hybrids as potential anticancer agents and process for the preparation thereof

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