- Design, synthesis, and antifibrosis evaluation of 4-(benzo-[c][1,2,5]thiadiazol-5-yl)-3(5)-(6-methyl- pyridin-2-yl)pyrazole and 3(5)-(6-methylpyridin- 2-yl)-4-(thieno-[3,2,-c]pyridin-2-yl)pyrazole derivatives
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Six series of 4-(benzo[c][1,2,5]thiadiazol-5-yl)-3(5)-(6-methylpyridin-2-yl)- pyrazoles 18a–d, 19a–d, 22a–d and 3(5)-(6-methylpyridin-2-yl)-4-(thieno[3,2,-c]- pyridin-2-yl)pyrazoles 20a–d, 21a–d, 23c, 23d have been synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activities in enzymatic assays. Among these compounds, the most active compound, 22c, inhibited ALK5 phosphorylation with an IC50 value of 0.030 μM in the enzymatic assay. Compound 22c showed four-fold more potent activity against ALK5 kinase than the clinical candidate, compound LY-2157299. The selectivity index of 22c against p38α MAP kinase is 235, which is much higher than that of LY-2157299 (4) and equally selective to that of EW-7197 (218). Compound 22c effectively suppressed protein and mRNA expression of collagen I and α-SMA in TGF-β-induced LX-2 human hepatic stellate cell (HSC), this result shows that compound 22c has the ability to inhibit the activation of HSC. Compound 22c is expected to be a preclinical candidate for the treatment of hepatic fibrosis.
- Zhu, Wen-Jing,Cui, Ben-Wen,Wang, Hui Min,Nan, Ji-Xing,Piao, Hu-Ri,Lian, Li-Hua,Jin, Cheng Hua
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- Rational design of novel CYP2A6 inhibitors
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Inhibition of CYP2A6-mediated nicotine metabolism can reduce cigarette smoking. We sought potent and selective CYP2A6 inhibitors to be used as leads for drugs useful in smoking reduction therapy, by evaluating CYP2A6 inhibitory effect of novel formyl, alk
- Tani, Niina,Juvonen, Risto O.,Raunio, Hannu,Fashe, Muluneh,Lepp?nen, Jukka,Zhao, Bin,Tyndale, Rachel F.,Rahnasto-Rilla, Minna
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p. 6655 - 6664
(2015/02/19)
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- Orally bioavailable highly potent HIV protease inhibitors against PI-resistant virus
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Efforts directed to identifying potent HIV protease inhibitors (PI) have yielded a class of compounds that are not only very active against wild-type (NL4-3) HIV virus but also very potent against a panel of PI-resistant viral isolates. Chemistry and biol
- Lu, Zhijian,Bohn, Joann,Rano, Tom,Rutkowski, Carrie A.,Simcoe, Amy L.,Olsen, David B.,Schleif, William A.,Carella, Anthony,Gabryelski, Lori,Jin, Lixia,Lin, Jiunn H.,Emini, Emilio,Chapman, Kevin,Tata, James R.
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p. 5311 - 5314
(2007/10/03)
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- HETEROCYCLIC COMPOUNDS, METHODS OF MAKING THEM AND THEIR USE IN THERAPY
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In part, the present invention is directed to antibacterial compounds of formula (I) wherein A is a bicyclic heteroaryl ring or a tricyclic ring and R2 is an heterocyclic residue; L is a bond, or L is alkyl, alkenyl or cycloalkyl.
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- Preparation of alkali metal thieno(furo)pyridines
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Thienopyridines and furopyridines react at the 2-position with non-nucleophilic alkali metal bases to give alkali metal thieno(furo)pyridine salts.
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