- Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB
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A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi- and extensive drug resistant Mtb strains. All the compounds, except 1o, 1p and 1q, showed potent anti-TB activity with MIC of 1-64 mg/L. The test of broad spectrum panel revealed that this series are specific to Mtb. The cytotoxicity assessment indicated that the compounds were not cytotoxic against HEK 293 cells. The compounds could have a novel mechanism to anti-Mtb as they can inhibit drug sensitive and drug resistant Mtb.
- Li, Dongsheng,Gao, Nana,Zhu, Ningyu,Lin, Yuan,Li, Yan,Chen, Minghua,You, Xuefu,Lu, Yu,Wan, Kanglin,Jiang, Jian-Dong,Jiang, Wei,Si, Shuyi
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p. 5178 - 5181
(2015/11/09)
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- Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats
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Starting from a known piperazine-based SCD-1 inhibitor, we obtained more potent benzoylpiperidine analogs. Optimization of the structure of the benzoylpiperidine-based SCD-1 inhibitors resulted in the identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-2-pyridin-3-yl-ethyl)amide (24) which showed strong inhibitory activity against both human and murine SCD-1. In addition, this compound exhibited good oral bioavailability and demonstrated plasma triglyceride lowering effects in Zucker fatty rats in a dose-dependent manner after a 7-day oral administration (qd).
- Uto, Yoshikazu,Ogata, Tsuneaki,Kiyotsuka, Yohei,Ueno, Yuko,Miyazawa, Yuriko,Kurata, Hitoshi,Deguchi, Tsuneo,Watanabe, Nobuaki,Konishi, Masahiro,Okuyama, Ryo,Kurikawa, Nobuya,Takagi, Toshiyuki,Wakimoto, Satoko,Ohsumi, Jun
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scheme or table
p. 341 - 345
(2010/04/05)
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- AMIDE COMPOUNDS
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The present invention provides compounds represented by the formula (Ie) and the formula (If) wherein each symbol is as defined in the specification. According to the present invention, these compounds have a DGAT inhibitory activity and are useful for the prophylaxis, treatment or improvement of diseases or pathologies caused by high expression or high activation of DGAT
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Page/Page column 147
(2008/06/13)
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- 1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones
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1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones of the formula STR1 wherein R is hydrogen or fluoro, R1 is hydrogen, fluoro chloro, bromo or trifluoromethyl, and n is 2 to 4, having anticonvulsant activity and useful as anti-anxiety agents, are disclosed.
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