ChemMedChem p. 1662 - 1668 (2019)
Update date:2022-08-03
Topics:
Sijm, Maarten
Siciliano de Araújo, Julianna
Ramos Llorca, Alba
Orrling, Kristina
Stiny, Lydia
Matheeussen, An
Maes, Louis
de Esch, Iwan J. P.
de Nazaré Correia Soeiro, Maria
Sterk, Geert Jan
Leurs, Rob
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.
View MoreChongqing Shuangfeng Chemical Co.,Ltd
Contact:+86-23-49850156
Address:No.663,xuanhua Rd,yongchuan,chongqing,China
Zhejiang Kangfeng Chemical Co.,LTD.
Contact:+86-579-86709687
Address:Xueshizhai Industrial Zone, Weishan Town,Dongyang City, Zhejiang Province ,China
zhenjiang runjing high purity chemical co ltd
Contact:+86-511-83361155
Address:No.8.haixi road,international chemical park
Hebei DaPeng Pharm & Chem Co., Ltd.
Contact:86-317-7298678,0576-88861898 88861908
Address:West Songmen Village, East Songmen Town, Wuqiao, Cangzhou, Hebei ,China
Hangzhou Taiyan Trading Co., Ltd(expird)
Contact:+86-13777583958
Address:NO.63, Xingyi Street, Xihu District, Hangzhou, Zhejiang, China
Doi:10.1248/cpb.32.5023
(1984)Doi:10.1002/jlcr.1141
(2006)Doi:10.1021/jo00210a008
(1985)Doi:10.1021/ja075725i
(2007)Doi:10.1002/jhet.5570440534
(2007)Doi:10.1007/s10593-005-0311-4
(2005)