Molecules (2020)
Update date:2022-08-11
Topics:
Adamecz, Dóra Izabella
Frank, éva
Kiricsi, Mónika
Krishna Gopisetty, Mohana
Molnár, Barnabás
Although the hormone independent cytotoxic activity of several estradiol derivatives endowed with a simple substituent at C-2 has been reported so far, 2-heterocyclic and 2,3-condensed analogs are less investigated from both synthetic and pharmacological points of view. Therefore, novel A-ring-connected 2-pyrazoles of estradiol and, for comparison, their structurally simplified non-steroidal pairs were synthesized from estradiol 3-methyl ether and 6-methoxy-1,2,3,4-tetrahydronaphthalene. Friedel-Crafts acetylation of the protected phenolic compounds and subsequent O-demethylation led to ortho-substituted derivatives regioselectively, which were converted to arylhydrazones with phenylhydrazine, 4-tolylhydrazine and 4-chloro-phenylhydrazine, respectively, under microwave conditions. The hydrazones were subjected to cyclization with the Vilsmeier-Haack reagent immediately after preparation and the ring closure/formylation sequence resulted in steroidal and non-steroidal 40-formylpyrazoles in moderate to good yields. During reductive transformations, 4-hydroxymethyl-pyrazoles were obtained, while oxidative lactonization of the 4-formylpyrazole moiety with the phenolic OH in the presence of the Jones reagent afforded A-ring-integrated pyrazolocoumarin hybrids and related analogs. Steroidal pyrazoles, which were produced as C-17 acetates due to acetylation of C-17 OH during the primary Friedel-Crafts reaction, underwent deacetylation in alkaline methanol to furnish 2-heterocyclic estradiol derivatives. Pharmacological studies revealed the overall and cancer cell-specific cytotoxicity of the derivatives and the half maximal inhibitory concentrations were obtained for the most promising compounds.
View MoreContact:18710867521(wechat)
Address:Rm10516,Galaxy Tech Building #2,No.25 Tangyan Rd,Hi-Tech Zone,Xi'an, China
Contact:852-29282288
Address:HONGKONG
Huangshan Honghui Pharm Technology Co., Ltd.
website:http://www.honghuichem.com
Contact:18855958372
Address:Qingshan Wan No.1,Nanyuan Kou,SheXian Huangshan City,Anhui Province
Fuxin Jintelai Fluorin Chemical Co., Ltd.
Contact:+86-0418-8229599
Address:, 7th Huagong Road, Fluorine industry development zone (Yimatu Town,Fumeng County),Fuxin City, Liaoning Province, China
SHANDONG AONA CHEMICAL CO.,LTD.
Contact:86-532-85762926
Address:LIUYUAN TOWN, ZAOZHUANG CITY, SHANGDONG PROVINCE.
Doi:10.1039/c39950001255
(1995)Doi:10.1007/s00706-017-2098-2
(2018)Doi:10.1021/ja0425738
(2005)Doi:10.1021/ja00866a029
(1962)Doi:10.1002/jhet.1737
(2014)Doi:10.1021/ie50242a016
(1930)