- Design and biological evaluation of phenyl imidazole analogs as hedgehog signaling pathway inhibitors
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The hedgehog (Hh) signaling pathway is involved in diverse aspects of cellular events. Aberrant activation of Hh signaling pathway drives oncogenic transformation for a wide range of cancers, and it is therefore a promising target in cancer therapy. In the principle of association and ring-opening, we designed and synthesized a series of Hh signaling pathway inhibitors with phenyl imidazole scaffold, which were biologically evaluated in Gli-Luc reporter assay. Compound 25 was identified to possess high potency with nanomolar IC50, and moreover, it preserved the inhibition against wild-type and drug-resistant Smo-overexpressing cells. A molecular modeling study of compound 25 expounded its binding mode to Smo receptor, providing a basis for the further structural modification of phenyl imidazole analogs.
- Sun, Chiyu,Zhang, Ying,Wang, Han,Yin, Zhengxu,Wu, Lingqiong,Huang, Yanmiao,Zhang, Wenhu,Wang, Youbing,Hu, Qibo
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p. 546 - 552
(2020/10/06)
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- Synthesis and evaluation of novel N-3-benzimidazolephenylbisamide derivatives for antiproliferative and Hedgehog pathway inhibitory activity
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A series of novel N-3-benzimidazolephenylbisamide derivatives bearing the 4-benzyloxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against MGC803, HT29, MKN45 and SW620 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of the target compounds exhibited higher efficacy against MGC803, HT29 and MKN45 cells, among which compound 7m displayed higher antiproliferative activity than vismodegib. Furthermore, compound 7m manifested better inhibition of the Hedgehog (Hh) signaling pathway in different Hh-related assays and may compete with boron-dipyrromethene (BODIPY)-cyclopamine for binding to the human smoothened (Smo) receptor. In addition, molecular docking studies suggested that compound 7m interacts very closely with the vismodegib docking pose through hydrogen bonds at the taladegib binding site of the Smo receptor.
- Sun, Chiyu,Li, Yangsheng,Shi, Ailong,Zhang, Jingzhou,Li, Yafei,Zhao, Mingming,Zhang, Lijuan,Zheng, Huachuan,Meng, Ying,Ding, Huaiwei,Song, Hongrui
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supporting information
p. 1137 - 1142
(2015/06/25)
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- CHEMICAL COMPOUNDS
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The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new sulfonamide Nav1.7 inhibitors of formula (I): or a pharmaceutically acceptable salt thereof, wherein X, Ar1, R1, R2, R3, R4 and R5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.
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Page/Page column 76
(2012/02/02)
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- Hypolipidemic analogues of ethyl 4 benzyloxybenzoate
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A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure-activity relationships are discussed in terms of cholesterol-lowering activity together with effects on body weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl 4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoate, and ethyl 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.
- Baggaley,Fears,Hindley,Morgan,Murrell,Thorne
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p. 1388 - 1393
(2007/10/05)
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