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. Author manuscript; available in PMC: 2017 Oct 8.
Published in final edited form as: Bioorg Med Chem. 2016 Apr 8;24(11):2530–2543. doi: 10.1016/j.bmc.2016.04.019

Table 2.

Activity of C-4 and C-5 substituted pyridazinones 13a–d and 29a–b.

graphic file with name nihms797219t2.jpg
Compd R hPMN[a] FPR1-HL60[a] FPR2-HL60[a] FPR3-HL60[a]
13a CH2CH3 0.34 ± 0.11 (115) 0.18 ± 0.004 (185) 0.061 ± 0.022 (35) 0.46 ± 0.014 (35)
13b CH2CH2CH3 N.A. N.A. N.A. N.A.
13c (CH2)3CH3 1.40 ± 0.8 (45) 3.6 ± 1.1 (65) 4.5 ± 1.3 (30) N.A.
13d (CH2)4CH3 5.70 ± 1.2 (55) 1.4 ± 0.34 (95) 0.19 ± 0.018 (115) N.A.
29a H 0.56 ± 0.12 (85) 0.24 ± 0.09 (120) 9.6 ± 2.0 (65) N.A.
29b - 4.31 ± 0.4 (60) 2.50 ± 0.7 (110) 8.10 ± 1.7 (75) N.A.
[a]

Values, expressed as EC50 (µM) and Efficacy (% in brackets) were evaluated in Ca2+ flux assay. EC50 values represent the average mean of three independent experiments and were determined by nonlinear regression analysis of the concentration-response curves (5–6 points) generated using GraphPad Prism 5 with 95% confidential interval (p < 0.05). Efficacy (in brackets) is expressed as % of the response induced by 5 nM fMLF in human polymorphonuclear neutrophils (hPMN) and FPR1-HL60 cells or by 5 nM WKYMVm in FPR2-HL60 and FPR3-HL60 cells.

[b]

N.A., no activity (no response was observed during first 2 min after addition of compounds under investigation) considering the limits of efficacy < 20% and EC50 < 50 µM.