Table 4.

Activity of pyridazinones in mouse neutrophils and mouse Fpr-transfected RBL cells.

Compd	mPMN[a]	mFpr1-RBL[a]	mFpr2-RBL[a]
8a	N.A.[b]	N.A.[b]	N.A.[b]
8b	8.4 ± 2.6 (75)	N.A.[b]	N.A.[b]
8c	N.A.[b]	N.A.[b]	N.A.[b]
8d	24.1 ± 6.1 (105)	N.A.[b]	N.A.[b]
8e	15.9 ± 4.9 (120)	N.A.[b]	N.A.[b]
8f	N.A.[b]	N.A.[b]	N.A.[b]
15	22.8 ± 6.4 (30)	N.A.[b]	N.A.[b]
19a	N.A.[b]	N.A.[b]	N.A.[b]
19b	N.A.[b]	N.A.[b]	N.A.[b]
20	1.0 ± 0.34 (100)	4.7 ± 1.3 (50)	N.A.[b]
24	13.5 ± 3.7 (50)	6.7 ± 2.1 (55)	9.4 ± 2.7 (65)
25	N.A.[b]	N.A.[b]	N.A.[b]
26	5.6 ± 2.4 (45)	N.A.[b]	N.A.[b]
27a	N.A.[b]	N.A.[b]	N.A.[b]
27b	6.0 ± 1.9 (80)	18.5 ± 4.1 (25)	18.3 ± 3.8 (35)

^[a]The EC₅₀ (µM) and Efficacy (% in brackets) were evaluated in Ca²⁺ flux assay. Values are expressed EC₅₀ presented as the average mean of three independent experiments, in which EC₅₀ values 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 WKYMVm in mouse polymorphonuclear neutrophils (mPMN) or RBL cells transfected with mouse Fpr1 (mFpr1-RBL) or Fpr2 (mFpr2-RBL).

^[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.