Journal of Medicinal Chemistry p. 320 - 324 (1992)
Update date:2022-08-03
Topics:
DeGraw
Christie
Colwell
Sirotnak
2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.
View MoreContact:+86-25-52346955
Address:199,JIANYE ROAD,NANJING,CHINA
Wuxi Forest Biological Co.,Ltd
Contact:+86-510-81602300
Address:Room 317,Building D, No.159 middle Chengjiang Road,Jiangyin Wuxi city.
website:http://www.uvchemkeys.com
Contact:0086-021-58785816
Address:RM2607 Building No.1 Guosheng, Lane 388, Zhongjiang Road, Putuo District, Shanghai 200062 China
puyang hongda shengdao new material co.,ltd.
Contact:+86-393- 4896278
Address:No.29 East Zhongyuan Road
Contact:+86-20-32051076
Address:1105,Building A, International Business Incubator,Science City
Doi:10.1002/chem.201201359
(2012)Doi:10.1515/chempap-2015-0125
(2015)Doi:10.1080/00304948.2010.514795
(2010)Doi:10.1246/bcsj.59.1403
(1986)Doi:10.1016/j.bmcl.2005.03.121
(2005)Doi:10.1002/ejoc.200601137
(2007)