Lewis, A Beresford, A Chambers, M S Clark, G Hartley, D C Hirst, K L Higashino, M Kawahadara, S Nakanishi, M Saito, T
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Published in
Bioorganic & medicinal chemistry letters
The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminati...
Moningka, Remond Anthony Romero, F Hastings, Nicholas B Guo, Zhiqiang Wang, Ming Di Salvo, Jerry Li, Ying Trusca, Dorina Deng, Qiaoling Tong, Vincent
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Published in
Bioorganic & medicinal chemistry letters
Here, we report the discovery of a new class of NPBWR1 antagonists identified from a fragment-based screen. Compound 1 (cAMP IC50 = 250 µM; LE = 0.29) emerged as an initial hit. Further optimization of 1 by SAR-by-catalogue and chemical modification produced 21a (cAMP IC50 = 30 nM; LE = 0.39) with a 6,700-fold increase in potency from fragment 1. S...
He, Yang Zhang, Yue Qin, Hai-Ying Gu, Dong-Yue Lu, Xiao Hu, Jin-Xi Ye, Wei-Liang He, Guang-Bin
Published in
Bioorganic & medicinal chemistry letters
The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU...
Ding, Sha Ghavami, Maryam Butler, Joshua H Merino, Emilio F Slebodnick, Carla Cassera, Maria B Carlier, Paul R
Published in
Bioorganic & medicinal chemistry letters
The antimalarial candidate MMV008138 (1a) is of particular interest because its target enzyme (IspD) is absent in human. To achieve higher potency, and to probe for steric demand, a series of analogs of 1a were prepared that featured methyl-substitution of the B- and C-rings, as well as ring-chain transformations. X-ray crystallography, NMR spectro...
Zhao, Yangyang Li, Huangong Sun, Pengwei Gao, Li Liu, Jingbo Zhou, Sha Xiong, Lixia Yang, Na Li, Yuxin Li, Zhengming
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Published in
Bioorganic & medicinal chemistry letters
In order to search for the new ryanodine receptor (RyR) regulator, a series of 35 novel fluoro-substituted compounds introduced 1-(2-chloro-4,5-difluorophenyl)-1H-pyrazole moiety containing modified pyrazole heterocycle were designed and synthesized. Then, they were tested for the insecticidal activities against Mythimna separata and Plutella xylos...
Zhang, Qing Zhao, Kuantao Zhang, Lixun Jiao, Xiaoyu Zhang, Yongjie Tang, Chunlei
Published in
Bioorganic & medicinal chemistry letters
As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in ...
Daher, Samer S Franklin, Kevin P Scherzi, Tyler Dunman, Paul M Andrade, Rodrigo B
Published in
Bioorganic & medicinal chemistry letters
Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a novel series analogs derived from ...
Blaikie, Laura Kay, Graeme Kong Thoo Lin, Paul
Published in
Bioorganic & medicinal chemistry letters
A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivit...
Sui, Xin Liu, Jishuang Xin, Yu Qu, Mo Qiu, Ye He, Tianzhu Luo, Haoming Wang, Weinan Qiu, Zhidong
Published in
Bioorganic & medicinal chemistry letters
25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum...
Eagon, Scott Hammill, Jared T Bach, Jordan Everson, Nikalet Sisley, Tyler A Walls, Michael J Durham, Sierra Pillai, Dylan R Falade, Mofolusho O Rice, Amy L
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Published in
Bioorganic & medicinal chemistry letters
A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitu...
