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Synthesis and biological evaluation of novel 2,4,5-triaryl-1 H-pyrazol-3(2H)-ones as inhibitors of ALK5

Synthesis and biological evaluation of novel 2,4,5-triaryl-1 H-pyrazol-3(2H)-ones as inhibitors of ALK5
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摘要 A series of 2,4,5-triaryl substituted 1H-pyrazol-3（2H）-ones,as ALK5 inhibitors,were desigened,synthesized and evaluated in vitro.Most compounds exhibited noticeable ALK5 inhibition activities at 1μmol/L and displayed no significant cytotoxicities at 30μmol/L. A series of 2,4,5-triaryl substituted 1H-pyrazol-3（2H）-ones,as ALK5 inhibitors,were desigened,synthesized and evaluated in vitro.Most compounds exhibited noticeable ALK5 inhibition activities at 1μmol/L and displayed no significant cytotoxicities at 30μmol/L.
作者 Xing Zhou Li Xian Ping Dai Kang Ying Lai Li Li Wang Zhi Bing Zheng Song Li
机构地区 Beijing Institute of Pharmacology ＆ Toxicology Beijing China School of Pharmaceutical Engineering Shenyang Pharmaceutical University Shenyang China
出处 《Chinese Chemical Letters》 SCIE CAS CSCD 2008年第4期379-382,共4页 中国化学快报（英文版）
关键词 Activin-like kinases5（ALK5） Kinase inhibitors 1H-Pyrazol-3（2H）-ones Activin-like kinases5（ALK5） Kinase inhibitors 1H-Pyrazol-3（2H）-ones
分类号 Q55 [生物学—生物化学] O626 [理学—有机化学]
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  • 1[1]J.Massague,S.A.Blain,R.S.Lo,et al.Cell 103 (2000) 295.
  • 2[2]J.F.Callahan,J.L.Burgess,J.A.Fornwald,et al.J.Med.Chem.45 (2002) 999.
  • 3[3]J.Singh,E.L.Leona,J.S.Sawyer,et al.Curr.Opin.Drug Disc.Dev.7 (2004) 437.
  • 4[4]S.E.de Laszlo,D.Visco,L.Agarwal,et al.Bioorg.Med.Chem.Lett.8 (1998) 2689.
  • 5[5]A.B.Smith,P.A.Levenberg,Synthesis (1981) 567.
  • 6[6]J.H.Hall,M.Gisler,J.Org.Chem.41 (1976) 3769.
  • 7[7]E Gellibert,A.C.de Gouville,J.Woolven,et al.J.Med.Chem.49 (2006) 2210.
  • 8[8]P.Mazzarino,G.Pietra,P.Vacca,et al.Eur.J.Immunol.35 (2005) 3240.
  • 9[9]7a:rap:202-204 ℃,1H NMR(400 MHz,DMSO-d6 δ ppm,J Hz) 6.02 (s,1H),6.06 (s,1H),6.79 (d,1 H,J=8.7 Hz),6.88 (s,1H),6.90 (d,1H,J=8.7 Hz),7.38 (d,1H,J=6.7 Hz),7.67 (d,1H,J=7.8 Hz),7.85 (dd,1H,J=7.8,6.7 Hz),8.00 (d,2H,J=8.7 Hz),8.10 (d,2H,J=8.7 Hz),8.56 (1H,s),11.66 (brs,1H,NH).EIMS (m/z,%) 382 (M+,100).8a:mp:248-252 ℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 6.01 (s,2H),6.80 (d,1H,J=7.8 Hz),6.87 (s,1H),6.89 (d,1H,J=7.8 Hz),7.36 (brs,1H),7.42 (brs,1H,NH),7.68 (m,1H),7.83 (dd,1H,J=7.8,7.3 Hz),7.94 (d,2H,J=8.68 Hz),8.01 (d,2H,J=8.7 Hz),8.04 (brs,1H,NH),8.53 (brs,1H),11.15 (brs,1H,NH).EIMS (m/z,%) 400 (M+,100).7b:mp:220-221 ℃,1H NMR(400 MHz,DMSO-d6,δ ppm,J Hz) 2.44 (s,3H),6.01 (s,2H),6.83 (dd,1H,J=7.8,I.12 Hz),6.88 (d,1H,J=7.8 Hz),6.96 (d,1H,J=1.1 Hz),7.25 (d,1H,J=7.3 Hz),7.39 (d,1H,J=7.8 Hz),7.72 (dd,1H,J=7.8,7.7 Hz),7.99 (d,2H,J=8.4 Hz),8.10 (d,2H,J=8.4 Hz),11.68 (brs,1H,NH).FABMS (m/z,%),397 (MH+,50).8b:mp:165-167 ℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz)2.42 (s,3H),6.00 (s,2H),6.84 (d,1H,J=8.2 Hz),6.86 (d,1H,J=8.16 Hz),6.97 (s,1H),7.21 (m,1H),7.38 (m,1H),7.40 (brs,1H,NH),7.69 (dd,1H,J=7.6,7.8 Hz),7.96 (d,2H,J=8.4 Hz),7.99 (d,2H,J=8.4 Hz),8.01 (brs,1H,NH),11.17 (brs,1H,NH).EIMS (m/z,%) 414 (M+,100).7c:mp:208-210 ℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 3.68 (s,3H),3.76 (s,3H),6.89 (d,1H,J=8.4 Hz),6.92 (d,1H,J=8.4 Hz),6.96 (s,1H),7.39 (m,1H),7.65 (m,1H),7.84 (m,1H),8.00 (d,2H,J=8.2 Hz),8.11 (d,2H,J=8.7 Hz),8.56 (brs,1H),11.5 (brs,1H).ESIMS (m/z,%)399 (M+,100).8d:1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 2.49 (s,3H),3.64 (s,3H),3.74 (s,3H),6.90 (d,1H,J=8.4 Hz),6.93 (d,1H,J=8.4 Hz),7.02 (s,1H),7.21 (d,1H,J=7.6 Hz),7.36 (d,IH,J=7.6 Hz),7.38 (brs,1H,NH),7.69 (dd,1H,J=7.6,7.6 Hz),7.99 (m,5H),11.17 (brs,1H,NH).ESIMS (m/z,%),429 (M+-H,30).7e:mp:204-206℃,1H NMR (400MHz,CDCl3,δ ppm,J Hz) 5.73 (s,3H),6.85 (d,2H,J=8.4 Hz),7.09-7.44 (m,6H),7.96 (d,2H,J=9.0 Hz),8.04 (d,2H,J=9.0 Hz),11.47 (brs,1H,NH),ESIMS (m/z,%),386 (MH+,100).8e:mp:259-261 ℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 3.73 (s,3H),6.88 (d,2H,J=7.9 Hz),7.07-7.54(m,9H),7.93 (d,2H,J=8.1 Hz),8.00 (d,2H,J=8.1Hz),8.02 (brs,1H,NH),11.13 (brs,1H,NH);FABMS (m/z,%),404 (MH+,100).7f:mp:233-235 ℃,1H NMR (400MHz,DMSO-d6,δ ppm,J Hz) 7.15 (dd,2H,J=8.9,8.9 Hz),7.17-7.31 (m,4H),7.40-7.60 (m,2H),8.01 (d,2H,J=8.9 Hz),8.08 (d,2H,J=8.9 Hz),11.67(brs,1H,NH).8f:mp:260-260℃,1H NMR(400 MHz,DMSO-d6,δ ppm,J Hz) 7.12 (dd,2H,J=8.4,8.9 Hz),7.19-7.30 (m,4H),7.41 (brs,1H,NH),7.47 (m,1H),7.54 (m,1H),7.94 (d,2H,J=8.9 Hz),8.00 (d,2H,J=8.9 Hz),8.03 (brs,1H,NH),11.42 (brs,1H,NH).EIMS (m/z,%),391(M+,100).7g:mp:186-188 ℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 6.03 (s,2H),6.97 (s,2H),6.95 (s,1H),7.25 (dd,2H,J=8.1,7.8 Hz),7.40 (m,2H),7.98 (d,2H,J=8.3 Hz),8.12 (d,2H,J=8.3 Hz).ESIMS (m/z,100),400 (MH+,100).8g:rap:275-277 ℃,1HNMR(400 MHz,DMSO-d6,δ ppm,J Hz) 6.00 (s,2H),6.87-6.98 (m,3H),7.21-7.30 (m,2H),7.35-7.46 (m,2H),7.9-8.05 (m,4H),6.05 (brs,1H,NH),7.05 (brs,1H,NH),11.43 (brs,1H,NH).FABMS (m/z,100),418 (MH+,50).7h:1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) 7.13-.21 (m,2H),7.23-7.27 (m,2H),7.31-7.47 (m,4H),8.00 (d,2H,J=8.9 Hz),8.12 (d,2H,J=8.9 Hz);FABMS (m/z,100),374 (MH+,100).8h:mp:288-290℃,1H NMR (400 MHz,DMSO-d6,δ ppm,J Hz) δ 7.13-7.21 (m,2H),7.25 (dd,2H,J=7.6,7.3 Hz),7.32-7.47 (m,5H),7.97 (d,2H,J=8.7 Hz),8.12 (d,2H,J=8.7 Hz),8.05 (brs,1H,NH),11.56 (brs,1H,NH);EIMS (m/z,100),391 (M+,100).
Chinese Chemical Letters
2008年 第4期

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